Universal nutrime pellet concept
166
OVERVIEW How genetic variants can disrupt protective systems in our body
description
How geneticvariants can disrupt protective systems in ourbody
Transcript of Universal nutrime pellet concept
OVERVIEW
How genetic variants candisrupt protective systems
in our body
MICRONUTRIENTS
Genes fulfill a number of protectiveroles in the body
OXIDATIVE STRESS
GPX1
SOD2
AGRESSIVE IMMUNE SYSTEM
TNFa
IL1A
REGULATE HOMOCYSTEINE
MTHFR
MTRR
REMOVE TOXINS FROM BODY
GSTM1
GSTT1
MICRONUTRIENTS
Genetic variants disrupt protective effect
OXIDATIVE STRESS
GPX1
SOD2
AGRESSIVE IMMUNE SYSTEM
TNFa
IL1A
REGULATE HOMOCYSTEINE
MTHFR
MTRR
REMOVE TOXINS FROM BODY
GSTM1
GSTT1
OVERVIEW
How micronutrients canrecover some of the lost
function
MICRONUTRIENTS
Certain micronutrients canrecover lost function
OXIDATIVE STRESS
GPX1
SOD2
AGRESSIVE IMMUNE SYSTEM
TNFa
IL1A
REGULATE HOMOCYSTEINE
MTHFR
MTRR
REMOVE TOXINS FROM BODY
GSTM1
GSTT1
Vit CVit E Vit A
ALA
Folic acid
Vit B12Vit B6
Selenium
Calcium
Iron
MICRONUTRIENTS
The concept Test 50+ genes and determine therequirement of 22 micronutrients
Bone HealthOsteoporosis (Calcium Vit D Magnesium)
Eye HealthMacular Degeneration (Antioxidants)
Heart healthCholesterol (Omega3)
Homocysteine (Folic acid B-Vitamins)
Food intolerancesLactose Intolerance (calcium)
Coeliac disease (Multivitamin)
Joint HealthRheumatoid Arthritis (Omega3)
Metabolic HealthIron overload disorder (Iron)
Cognitive HealthAlzheimers disease (Antioxidants)
DetoxificationHeavy metals (Calcium Selenium Iron)
OVERVIEW
One example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD2
SOD1
SOD3
5 of oxygen
Mitochondria
5 of oxygen becomes Superoxide a free radical 3 genes protect the cell in various locations from these damaging
chain reactions
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
27 of the population has a geneticvariant in this gene abolishing its
protective effect
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Superoxide damages cells and speedsup ageing and disease development
Free radicals
OXIDATIVE STRESS
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
Antioxidants can help neutralize freeradicals before they do any harm if
available in the right quantities
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
The lost protection from superoxidecan be recovered
OXIDATIVE STRESS
Free radicals damage cells
SOD2
SOD2
Vit CVit E
ALAVit A eg100mg
If SOD2 is active itprotects the cells Only
normal amounts ofantioxidants are required
OXIDATIVE STRESS
Free radicals damage cells
SOD2SOD2
SOD2
Vit CVit E
ALAVit A
Vit CVit E
ALAVit Aeg100mg
eg300mg
If SOD2 is deactivated theprotective function is lost
Higher antioxidant dosagesare necessary
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
MICRONUTRIENTS
Genes fulfill a number of protectiveroles in the body
OXIDATIVE STRESS
GPX1
SOD2
AGRESSIVE IMMUNE SYSTEM
TNFa
IL1A
REGULATE HOMOCYSTEINE
MTHFR
MTRR
REMOVE TOXINS FROM BODY
GSTM1
GSTT1
MICRONUTRIENTS
Genetic variants disrupt protective effect
OXIDATIVE STRESS
GPX1
SOD2
AGRESSIVE IMMUNE SYSTEM
TNFa
IL1A
REGULATE HOMOCYSTEINE
MTHFR
MTRR
REMOVE TOXINS FROM BODY
GSTM1
GSTT1
OVERVIEW
How micronutrients canrecover some of the lost
function
MICRONUTRIENTS
Certain micronutrients canrecover lost function
OXIDATIVE STRESS
GPX1
SOD2
AGRESSIVE IMMUNE SYSTEM
TNFa
IL1A
REGULATE HOMOCYSTEINE
MTHFR
MTRR
REMOVE TOXINS FROM BODY
GSTM1
GSTT1
Vit CVit E Vit A
ALA
Folic acid
Vit B12Vit B6
Selenium
Calcium
Iron
MICRONUTRIENTS
The concept Test 50+ genes and determine therequirement of 22 micronutrients
Bone HealthOsteoporosis (Calcium Vit D Magnesium)
Eye HealthMacular Degeneration (Antioxidants)
Heart healthCholesterol (Omega3)
Homocysteine (Folic acid B-Vitamins)
Food intolerancesLactose Intolerance (calcium)
Coeliac disease (Multivitamin)
Joint HealthRheumatoid Arthritis (Omega3)
Metabolic HealthIron overload disorder (Iron)
Cognitive HealthAlzheimers disease (Antioxidants)
DetoxificationHeavy metals (Calcium Selenium Iron)
OVERVIEW
One example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD2
SOD1
SOD3
5 of oxygen
Mitochondria
5 of oxygen becomes Superoxide a free radical 3 genes protect the cell in various locations from these damaging
chain reactions
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
27 of the population has a geneticvariant in this gene abolishing its
protective effect
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Superoxide damages cells and speedsup ageing and disease development
Free radicals
OXIDATIVE STRESS
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
Antioxidants can help neutralize freeradicals before they do any harm if
available in the right quantities
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
The lost protection from superoxidecan be recovered
OXIDATIVE STRESS
Free radicals damage cells
SOD2
SOD2
Vit CVit E
ALAVit A eg100mg
If SOD2 is active itprotects the cells Only
normal amounts ofantioxidants are required
OXIDATIVE STRESS
Free radicals damage cells
SOD2SOD2
SOD2
Vit CVit E
ALAVit A
Vit CVit E
ALAVit Aeg100mg
eg300mg
If SOD2 is deactivated theprotective function is lost
Higher antioxidant dosagesare necessary
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
MICRONUTRIENTS
Genetic variants disrupt protective effect
OXIDATIVE STRESS
GPX1
SOD2
AGRESSIVE IMMUNE SYSTEM
TNFa
IL1A
REGULATE HOMOCYSTEINE
MTHFR
MTRR
REMOVE TOXINS FROM BODY
GSTM1
GSTT1
OVERVIEW
How micronutrients canrecover some of the lost
function
MICRONUTRIENTS
Certain micronutrients canrecover lost function
OXIDATIVE STRESS
GPX1
SOD2
AGRESSIVE IMMUNE SYSTEM
TNFa
IL1A
REGULATE HOMOCYSTEINE
MTHFR
MTRR
REMOVE TOXINS FROM BODY
GSTM1
GSTT1
Vit CVit E Vit A
ALA
Folic acid
Vit B12Vit B6
Selenium
Calcium
Iron
MICRONUTRIENTS
The concept Test 50+ genes and determine therequirement of 22 micronutrients
Bone HealthOsteoporosis (Calcium Vit D Magnesium)
Eye HealthMacular Degeneration (Antioxidants)
Heart healthCholesterol (Omega3)
Homocysteine (Folic acid B-Vitamins)
Food intolerancesLactose Intolerance (calcium)
Coeliac disease (Multivitamin)
Joint HealthRheumatoid Arthritis (Omega3)
Metabolic HealthIron overload disorder (Iron)
Cognitive HealthAlzheimers disease (Antioxidants)
DetoxificationHeavy metals (Calcium Selenium Iron)
OVERVIEW
One example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD2
SOD1
SOD3
5 of oxygen
Mitochondria
5 of oxygen becomes Superoxide a free radical 3 genes protect the cell in various locations from these damaging
chain reactions
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
27 of the population has a geneticvariant in this gene abolishing its
protective effect
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Superoxide damages cells and speedsup ageing and disease development
Free radicals
OXIDATIVE STRESS
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
Antioxidants can help neutralize freeradicals before they do any harm if
available in the right quantities
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
The lost protection from superoxidecan be recovered
OXIDATIVE STRESS
Free radicals damage cells
SOD2
SOD2
Vit CVit E
ALAVit A eg100mg
If SOD2 is active itprotects the cells Only
normal amounts ofantioxidants are required
OXIDATIVE STRESS
Free radicals damage cells
SOD2SOD2
SOD2
Vit CVit E
ALAVit A
Vit CVit E
ALAVit Aeg100mg
eg300mg
If SOD2 is deactivated theprotective function is lost
Higher antioxidant dosagesare necessary
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
How micronutrients canrecover some of the lost
function
MICRONUTRIENTS
Certain micronutrients canrecover lost function
OXIDATIVE STRESS
GPX1
SOD2
AGRESSIVE IMMUNE SYSTEM
TNFa
IL1A
REGULATE HOMOCYSTEINE
MTHFR
MTRR
REMOVE TOXINS FROM BODY
GSTM1
GSTT1
Vit CVit E Vit A
ALA
Folic acid
Vit B12Vit B6
Selenium
Calcium
Iron
MICRONUTRIENTS
The concept Test 50+ genes and determine therequirement of 22 micronutrients
Bone HealthOsteoporosis (Calcium Vit D Magnesium)
Eye HealthMacular Degeneration (Antioxidants)
Heart healthCholesterol (Omega3)
Homocysteine (Folic acid B-Vitamins)
Food intolerancesLactose Intolerance (calcium)
Coeliac disease (Multivitamin)
Joint HealthRheumatoid Arthritis (Omega3)
Metabolic HealthIron overload disorder (Iron)
Cognitive HealthAlzheimers disease (Antioxidants)
DetoxificationHeavy metals (Calcium Selenium Iron)
OVERVIEW
One example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD2
SOD1
SOD3
5 of oxygen
Mitochondria
5 of oxygen becomes Superoxide a free radical 3 genes protect the cell in various locations from these damaging
chain reactions
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
27 of the population has a geneticvariant in this gene abolishing its
protective effect
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Superoxide damages cells and speedsup ageing and disease development
Free radicals
OXIDATIVE STRESS
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
Antioxidants can help neutralize freeradicals before they do any harm if
available in the right quantities
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
The lost protection from superoxidecan be recovered
OXIDATIVE STRESS
Free radicals damage cells
SOD2
SOD2
Vit CVit E
ALAVit A eg100mg
If SOD2 is active itprotects the cells Only
normal amounts ofantioxidants are required
OXIDATIVE STRESS
Free radicals damage cells
SOD2SOD2
SOD2
Vit CVit E
ALAVit A
Vit CVit E
ALAVit Aeg100mg
eg300mg
If SOD2 is deactivated theprotective function is lost
Higher antioxidant dosagesare necessary
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
MICRONUTRIENTS
Certain micronutrients canrecover lost function
OXIDATIVE STRESS
GPX1
SOD2
AGRESSIVE IMMUNE SYSTEM
TNFa
IL1A
REGULATE HOMOCYSTEINE
MTHFR
MTRR
REMOVE TOXINS FROM BODY
GSTM1
GSTT1
Vit CVit E Vit A
ALA
Folic acid
Vit B12Vit B6
Selenium
Calcium
Iron
MICRONUTRIENTS
The concept Test 50+ genes and determine therequirement of 22 micronutrients
Bone HealthOsteoporosis (Calcium Vit D Magnesium)
Eye HealthMacular Degeneration (Antioxidants)
Heart healthCholesterol (Omega3)
Homocysteine (Folic acid B-Vitamins)
Food intolerancesLactose Intolerance (calcium)
Coeliac disease (Multivitamin)
Joint HealthRheumatoid Arthritis (Omega3)
Metabolic HealthIron overload disorder (Iron)
Cognitive HealthAlzheimers disease (Antioxidants)
DetoxificationHeavy metals (Calcium Selenium Iron)
OVERVIEW
One example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD2
SOD1
SOD3
5 of oxygen
Mitochondria
5 of oxygen becomes Superoxide a free radical 3 genes protect the cell in various locations from these damaging
chain reactions
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
27 of the population has a geneticvariant in this gene abolishing its
protective effect
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Superoxide damages cells and speedsup ageing and disease development
Free radicals
OXIDATIVE STRESS
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
Antioxidants can help neutralize freeradicals before they do any harm if
available in the right quantities
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
The lost protection from superoxidecan be recovered
OXIDATIVE STRESS
Free radicals damage cells
SOD2
SOD2
Vit CVit E
ALAVit A eg100mg
If SOD2 is active itprotects the cells Only
normal amounts ofantioxidants are required
OXIDATIVE STRESS
Free radicals damage cells
SOD2SOD2
SOD2
Vit CVit E
ALAVit A
Vit CVit E
ALAVit Aeg100mg
eg300mg
If SOD2 is deactivated theprotective function is lost
Higher antioxidant dosagesare necessary
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
MICRONUTRIENTS
The concept Test 50+ genes and determine therequirement of 22 micronutrients
Bone HealthOsteoporosis (Calcium Vit D Magnesium)
Eye HealthMacular Degeneration (Antioxidants)
Heart healthCholesterol (Omega3)
Homocysteine (Folic acid B-Vitamins)
Food intolerancesLactose Intolerance (calcium)
Coeliac disease (Multivitamin)
Joint HealthRheumatoid Arthritis (Omega3)
Metabolic HealthIron overload disorder (Iron)
Cognitive HealthAlzheimers disease (Antioxidants)
DetoxificationHeavy metals (Calcium Selenium Iron)
OVERVIEW
One example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD2
SOD1
SOD3
5 of oxygen
Mitochondria
5 of oxygen becomes Superoxide a free radical 3 genes protect the cell in various locations from these damaging
chain reactions
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
27 of the population has a geneticvariant in this gene abolishing its
protective effect
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Superoxide damages cells and speedsup ageing and disease development
Free radicals
OXIDATIVE STRESS
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
Antioxidants can help neutralize freeradicals before they do any harm if
available in the right quantities
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
The lost protection from superoxidecan be recovered
OXIDATIVE STRESS
Free radicals damage cells
SOD2
SOD2
Vit CVit E
ALAVit A eg100mg
If SOD2 is active itprotects the cells Only
normal amounts ofantioxidants are required
OXIDATIVE STRESS
Free radicals damage cells
SOD2SOD2
SOD2
Vit CVit E
ALAVit A
Vit CVit E
ALAVit Aeg100mg
eg300mg
If SOD2 is deactivated theprotective function is lost
Higher antioxidant dosagesare necessary
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
One example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD2
SOD1
SOD3
5 of oxygen
Mitochondria
5 of oxygen becomes Superoxide a free radical 3 genes protect the cell in various locations from these damaging
chain reactions
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
27 of the population has a geneticvariant in this gene abolishing its
protective effect
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Superoxide damages cells and speedsup ageing and disease development
Free radicals
OXIDATIVE STRESS
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
Antioxidants can help neutralize freeradicals before they do any harm if
available in the right quantities
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
The lost protection from superoxidecan be recovered
OXIDATIVE STRESS
Free radicals damage cells
SOD2
SOD2
Vit CVit E
ALAVit A eg100mg
If SOD2 is active itprotects the cells Only
normal amounts ofantioxidants are required
OXIDATIVE STRESS
Free radicals damage cells
SOD2SOD2
SOD2
Vit CVit E
ALAVit A
Vit CVit E
ALAVit Aeg100mg
eg300mg
If SOD2 is deactivated theprotective function is lost
Higher antioxidant dosagesare necessary
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD2
SOD1
SOD3
5 of oxygen
Mitochondria
5 of oxygen becomes Superoxide a free radical 3 genes protect the cell in various locations from these damaging
chain reactions
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
27 of the population has a geneticvariant in this gene abolishing its
protective effect
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Superoxide damages cells and speedsup ageing and disease development
Free radicals
OXIDATIVE STRESS
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
Antioxidants can help neutralize freeradicals before they do any harm if
available in the right quantities
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
The lost protection from superoxidecan be recovered
OXIDATIVE STRESS
Free radicals damage cells
SOD2
SOD2
Vit CVit E
ALAVit A eg100mg
If SOD2 is active itprotects the cells Only
normal amounts ofantioxidants are required
OXIDATIVE STRESS
Free radicals damage cells
SOD2SOD2
SOD2
Vit CVit E
ALAVit A
Vit CVit E
ALAVit Aeg100mg
eg300mg
If SOD2 is deactivated theprotective function is lost
Higher antioxidant dosagesare necessary
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
27 of the population has a geneticvariant in this gene abolishing its
protective effect
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Superoxide damages cells and speedsup ageing and disease development
Free radicals
OXIDATIVE STRESS
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
Antioxidants can help neutralize freeradicals before they do any harm if
available in the right quantities
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
The lost protection from superoxidecan be recovered
OXIDATIVE STRESS
Free radicals damage cells
SOD2
SOD2
Vit CVit E
ALAVit A eg100mg
If SOD2 is active itprotects the cells Only
normal amounts ofantioxidants are required
OXIDATIVE STRESS
Free radicals damage cells
SOD2SOD2
SOD2
Vit CVit E
ALAVit A
Vit CVit E
ALAVit Aeg100mg
eg300mg
If SOD2 is deactivated theprotective function is lost
Higher antioxidant dosagesare necessary
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Superoxide damages cells and speedsup ageing and disease development
Free radicals
OXIDATIVE STRESS
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
Antioxidants can help neutralize freeradicals before they do any harm if
available in the right quantities
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
The lost protection from superoxidecan be recovered
OXIDATIVE STRESS
Free radicals damage cells
SOD2
SOD2
Vit CVit E
ALAVit A eg100mg
If SOD2 is active itprotects the cells Only
normal amounts ofantioxidants are required
OXIDATIVE STRESS
Free radicals damage cells
SOD2SOD2
SOD2
Vit CVit E
ALAVit A
Vit CVit E
ALAVit Aeg100mg
eg300mg
If SOD2 is deactivated theprotective function is lost
Higher antioxidant dosagesare necessary
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Free radicals
OXIDATIVE STRESS
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
Antioxidants can help neutralize freeradicals before they do any harm if
available in the right quantities
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
The lost protection from superoxidecan be recovered
OXIDATIVE STRESS
Free radicals damage cells
SOD2
SOD2
Vit CVit E
ALAVit A eg100mg
If SOD2 is active itprotects the cells Only
normal amounts ofantioxidants are required
OXIDATIVE STRESS
Free radicals damage cells
SOD2SOD2
SOD2
Vit CVit E
ALAVit A
Vit CVit E
ALAVit Aeg100mg
eg300mg
If SOD2 is deactivated theprotective function is lost
Higher antioxidant dosagesare necessary
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
Antioxidants can help neutralize freeradicals before they do any harm if
available in the right quantities
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
The lost protection from superoxidecan be recovered
OXIDATIVE STRESS
Free radicals damage cells
SOD2
SOD2
Vit CVit E
ALAVit A eg100mg
If SOD2 is active itprotects the cells Only
normal amounts ofantioxidants are required
OXIDATIVE STRESS
Free radicals damage cells
SOD2SOD2
SOD2
Vit CVit E
ALAVit A
Vit CVit E
ALAVit Aeg100mg
eg300mg
If SOD2 is deactivated theprotective function is lost
Higher antioxidant dosagesare necessary
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Free radicals damage cells
CYTOPLASMOF A CELL
Superoxide
Hydrogen-Peroxide
SOD1
SOD3
5 of oxygen
Mitochondria
Vit C
Vit E
Vit A
ALA
Vit C
ALA
ALA
Vit A
Vit A
The lost protection from superoxidecan be recovered
OXIDATIVE STRESS
Free radicals damage cells
SOD2
SOD2
Vit CVit E
ALAVit A eg100mg
If SOD2 is active itprotects the cells Only
normal amounts ofantioxidants are required
OXIDATIVE STRESS
Free radicals damage cells
SOD2SOD2
SOD2
Vit CVit E
ALAVit A
Vit CVit E
ALAVit Aeg100mg
eg300mg
If SOD2 is deactivated theprotective function is lost
Higher antioxidant dosagesare necessary
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Free radicals damage cells
SOD2
SOD2
Vit CVit E
ALAVit A eg100mg
If SOD2 is active itprotects the cells Only
normal amounts ofantioxidants are required
OXIDATIVE STRESS
Free radicals damage cells
SOD2SOD2
SOD2
Vit CVit E
ALAVit A
Vit CVit E
ALAVit Aeg100mg
eg300mg
If SOD2 is deactivated theprotective function is lost
Higher antioxidant dosagesare necessary
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Free radicals damage cells
SOD2SOD2
SOD2
Vit CVit E
ALAVit A
Vit CVit E
ALAVit Aeg100mg
eg300mg
If SOD2 is deactivated theprotective function is lost
Higher antioxidant dosagesare necessary
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
Another example of howgenetics influence
micronutrientrequirement
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1
Free Radical
The GPX1 gene producesan enzyme that protectsfrom oxidative stress as
well
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
GPX1 ndash a Selenoprotein neutralizingfree radicals
GPX1
GPX1Selenium
Free Radical
GPX1 is a selenoprotein meaning it needs dietary
selenium to work
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Free Radical
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
GPX1
GPX1
Neutralized
Selenium
GPX1 ndash a Selenoprotein neutralizingfree radicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
As selenium is required forGPX1 activity seleniumdeficiency causes low
activity and low protection
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Selenium deficiency and GPX1 activity
Selenium deficient30 activity
More Selenium70 activity
Adding more selenium hasbeen shown to increaseGPX1 activity and hence
protection from oxidative stress
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Polymorphism in the GPX1 gene
GPX1
GPX1
Free Radical
7 of the populationcarries a genetic variant that makes the enzyme
lass effective
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
GPX1
GPX1
Selenium
Polymorphism in the GPX1 gene
Free Radical
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
GPX1
GPX1
Weaker binding(eg 50 weaker)
Selenium
Polymorphism in the GPX1 gene
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Selenium normal35 activity
Selenium deficiency and GPX1 activity
Even with normal seleniumlevels the overall activity is
low in carriers of thisgenetic variant
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Selenium normal35 activity
MORE Selenium60 Activity
Selenium deficiency and GPX1 activity
Increasing selenium levelsto above normal levels
recovers the lackingfunction of the enzyme
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1
55 microg Day
If the person carries a functional GPX1-Gene he
receives the normal RDA asrecommended by official
agencies to be applicable toeveryone
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Dosage based on genetics
GPX1GPX1
55 microg Day 96 microg Day
If the gene carries thevariant we increase
selenium levels to recoverthe lost activity
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
An example how somenutrients can have no
effect
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10 Q10 ndash No effect
Coenzyme Q10 has noantioxidant effect by itself
and yet it is one of themost expensive
Micronutrient available
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI
Q10 ndash No effect
UbiquinolOxidative protection
The NQO1 Gene first must produce an enzymeconverting inactive
Coenzyme Q10 to activeUbiquinol
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Coenzyme Q10 needs to be activated
Q10
NQO1
Q10
UBI Free radical
Q10 ndash No effect
UbiquinolOxidative protection
UBI
Ubiquinol is a very potent free radical inhibitor
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Free radicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Q10 ndash No effect
Q10Due to a genetic variant 30 of the population
have less activity and 4 have no activity of the
NQO1 gene
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
FreeRadicals
Q10 ndash No effect
Q10
Free radicals accumulateand damage the cells
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No effect
Q10
UBI
UBI
UBI
UBI UBI
UBI
UBI
The only way to recoverthis function is through
ingesting active Ubiquinol as supplement
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Coenzyme Q10
Q10
NQO1
Free Radicals
Q10 ndash No Effect
Q10
C
E
ALA
C
E
E ALAC
ALA
E
Alternatively otherantioxidants in higher
dosages can protect fromfree radicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1
Q10
People with active NQO1 genes can use Coenzyme
Q10 as antioxidative support
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OXIDATIVE STRESS
Free radicals damage cells
NQO1NQO1
Q10
Q10 UBIC
E
ALA
People with inactive NQO1 genes require Ubiquinol
andor other antioxidantsto recover lost function
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
One example wheremicronutrient supply
through food might be toolow
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
LACTOSE INTOLERANCE
Genetics of Lactose intolerance
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
GENETICS
Normal process in a baby
GLU
Lactase-Gene
GLU
Lactose can not be absorbedin the intestine
LactASE enzyme splits lactoseinto smaller absorbable sugars
Galactose
Glucose
Babies produce thisenzyme throughout the
first years of their life to beable to digest milk
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
GENETICS
GLU
Lactase-Gene
GLU
Age++
Normal process in an adult
Lactose is food sourcefor bacteria
Gene is deactivatedwith increasing age
Evolutionarily Adult (cavemen) had no access to milk neededno enzyme and so productionwas gradually swithed off with
increasing age
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
GENETICS
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
10 20 30 40 50 60 70
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
Lactose intolerance ndash a normal process in adults
The normal process is a gradual decreasein enzyme production
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
GENETICS
GLU
Lactase-Gene
GLU
Age++
SNP
Genetic variant causing Lactose TOLERANCE in adulthood
Genetic variant disruptsbdquoAge-Deactivationldquo
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Intermediate Symptoms
Severe symptoms
Light symptoms
Lact
ase
-En
zym
e
Age (Years)
1 in 6 caucasians Lactase enzyme is deactivated
Lactose intolerance
GENETIK
10 20 30 40 50 60 70
5 of 6 caucasians Lactase enzyme is produced throughout life
Lactose intolerance
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
GENETICS
How did lactose intolerance arise
Genetic variationarose in one
person in northern Europe 10 000
years ago
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Famine causedmany people to die
GENETICS
How did lactose intolerance arise
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Milk as additional source of food =
Survival amp procreationAdvantage
GENETICS
How did lactose intolerance arise
80 of europeans todaycarry this one genetic
variant that arose back then
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance ishence only a
europeanphenomenon
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Lactose tolerance
Lactose INtolerance
GENETICS
How did lactose intolerance arise
Lactose tolerance was spread through
colonization andemigration from
europe
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through food
Lactose tolerant individuals thend to
have a higher calciumintake and cover muchof their requirementthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
= 600mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
Since the RDA applicable toeveryone is 800mg some peopledont get quite enough from theirnutrition and would benefit from
supplementation
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca 200mgday
= 800mg calciumday
People with a geneticvariant in the LCT gene eatno milk products and ingest
significantly less calciumthrough their diet
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
GENETICS
Consequence for micronutrient dosing
Lactase-GeneAge++
LACTOSE TOLERANT
Lactase-GeneAge++
LACTOSE INTOLERANT
= 600mg calcium
through food
= 30mg calcium
through foodCalcium RDA800mgday
Ca
Ca
Ca
Ca Ca
CaCaCa
Ca
200mgday 770mgday
= 800mg calciumday
A higher supplementation isrequired to reach the RDA
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
One example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
GENETICS
Next question Is the RDA enough
Osteoporosis ndash brittle bones
The question is is the RDA enough or might somepeople need even more
calcium
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with ageBone density tends to
increase up to the age of 30 and then gradually decrease
with age
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
Normal process Bonedensity decreases slightly
with age
Genetic variants Bonedensity is lost rapidly
Genetic variants increasebone mineral density loss
with increasing age Prevention is required
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
PREVENTION
10 20 30 40 50 60 70
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OSTEOPOROSIS
Bone density and age
Osteoporosis
Osteopenia
Bo
ne
min
era
lde
nsi
ty
Age (Years)
10 20 30 40 50 60 70
PREVENTION
As with saving money prevention must be started
as early as possible to beeffective
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg RDA according to EFSAThe European food safetyagency (EFSA) states the
RDA of calcium to be800mg This applies to
everyone
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA
In scientific studies 1200mg have been shown to beprotective and reduce
fracture risk
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
A person with ni genetic riskfor osteoporosis should
follow the RDA
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OSTEOPOROSIS
What dose of calcium is optimal
0 mg
1500 mg
800 mg
1200 mgKnown to be effectivein scientific studies
RDA according to EFSA800mgaverage (low) risk
1200mgmaximum (high) risk
A person with high osteoporosisrisk should follow the dosages we
know to be protective fromosteoporosis
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
Another example whererequirement of
micronutrient might behigher than normal
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
GENETICS
Next question Is the RDA enough
Heavy metal detoxification
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal
Enzymaticmodification
Neutralized
GSTM1
GSTT1
GSTP1
Removedthroughkidneys
In Phase 2 detoxification toxins are modified and
removed from the body byGST Genesenzymes
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Toxicity Cancer etc
Not neutralized60 of the population haveat least one of these genes
deactivated through geneticvariants Toxins such as lead
are not neutralized
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
PHASE 2 DETOXIFICATION
Enzymes remove heavy metals from body
Heavy metal GSTM1
GSTT1
GSTP1
Calcium bindstoxins
Ca
Ca
Ca
Calcium supplementation
binds Lead
Removedthroughkidneys
Calcium has been shown tobind and remove lead fromthe body Hence calcium
supplementation canrecover lost function
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
How different ceneticfactors collectively
determine the optimal dose of a micronutrient
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
CALCIUM
What influences the optimal calcium amount
Lactose Intolerant
OsteoporosisRisk
Detoxificationdeficiency
Recommended RDA
800 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+150 mg
NO+0 mg
YES+100 mg
=800mg
YES+150 mg
YES+150 mg
YES+100 mg
YES+150 mg
YES+150 mg
YES+100 mg
NO+0 mg
NO+0 mg
NO+0 mg
=1050mg
=950mg
=1200mg
Depending on genetic type the calcium amount can be
increased
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
One example where onemicronutrient has oneeffect in some and the
opposite effect in otherpeople
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OMEGA 3 fatty acids
An observation doctors frequently make
Person 1 with high cholesterol
Doctor recommends Omega3 supplements
Cholesterol improves
Most people assume fish oilcapsules (omega 3) are
beneficial for cholesterolund some are in fact right
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
In some cases the oppositehappens HDL Cholesterol
becomes worse
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OMEGA 3 fatty acids
An observation doctors frequently make
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves Cholesterol becomes worse
What is the reason
APOA1 (AA) APOA1 (GG)
This is caused by different genetic variations in the
APOA1 gene
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OMEGA 3 fatty acids
What is the consequence
Person 2 with high cholesterolPerson 1 with high cholesterol
Doctor recommends Omega3 supplementsDoctor recommends Omega3 supplements
Cholesterol improves
APOA1 (AA) APOA1 (GG)
Doctor recommends Phytosterols
Cholesterol improves
Different micronutrients required toachieve same result
Usind phytosterols insteadof Omega-3 achieves the
same cholesterol-improvingeffect
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
RDA 250 mg
Amounts shown to be effective 1000-2900mg
The RDA for Omega-3 isonly 250mg Far below the
dosages shown to beeffective in scientific
studies
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OMEGA 3 fatty acids
What daily dose is effective forimproving HDL Cholesterol
0 mg
3000 mg
250mg
1000mg
1500mg
2900mg Study 3
Study 1
Study 2
RDA according to EFSA
Range accepted to besufficient for general
population with average risk=RDA
Ranges known to be effectiveamong (also high risk)
individuals
Daily dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
Genes thatinfluence HDL
cholesterol levels
In this case there is nogenetic predisposition forbad HDL cholesterol levels
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1250mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of the beneficialvariant then Omega3 can
be recommended at the lowriskRDA dose
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 reverses the effectof Omega3 fatty acids thealternative Phytosterolsshould be used instead
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
Genes thatinfluence HDL
cholesterol levels
Certain genes causebad HDL cholesterol
levels Strongerintervention neessary
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1 1500mgOMEGA3
Genes thatinfluence HDL
cholesterol levels
If APOA1 is beneficial high doses of OMEGA 3 are recommended
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
CHOLESTEROL
Cholesterol is influenced by genes
CETP
APOA5
HDL Cholesterol
OK
APOA1
APOA1
250mgOMEGA3
250mgPhytoster
CETP
APOA5
HDL Cholesterol
Too low
APOA1
APOA1
1500mgOMEGA3
1500mgPhytoster
Genes thatinfluence HDL
cholesterol levels
If APOA1 is of thenegative type high
doses of thealternative are given
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
To summarize these fewexamples
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
SUMMARY
Genes influence the requirement ofMicronutrients
Genes influence micronutrient effect
Genes influence micronutrient dosage requirement
By testing 50+ genes we can dose 22 micronutrients based on genes
With 52 genes there are 717 000 000 000 000 000 000 000 possible results
Each micronutrient recipe is UNIQUE
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
How can one follow a specific micronutrient
recipe
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Use standard supplements
Individual gelatin capsules
Microtransporter method
Dose always toohigh or too low
Very expensive toproduce
Easy to mixEasy to automateEvery mix possibleCheap to produce
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
CONCEPT OF NUTRIENTS
How can you follow such variable recommendations
Vitamin C mix50 ww
Vitamin A mix4 ww
Zink mix11 ww
Mixture for one genetic
profile
38g6g 22g
Instructions ingest 8gday
Zink mix
Vitamin A mix
Vitamin C mix
Molecule of fillerMolecule of Vitamin CMolecule of Vitamin AMolecule of Zink
Amounts differ depending on genetic profile
We simply add differentamounts of differentpellet types to a mixture mix and then instructto take one spoon per day
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
NUTRIME
Pellets taken with spoon
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
What is the status of theproduct
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
STATUS
The status of the project
Patent pending (worldwide)
Genetic test ready (50+genes)
Microtransporters developed (23 different types)
Label and instructions completed
Product ready for launch
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
NUTRIME
Materials so far
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
NUTRIME
Materials so far
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
What can we offer
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OFFER
What we can offer AMWAY
Genetic test to be performed for each individual (Ready to launch)
Report booklet (digital or high quality print and post) describing results
Highest level of certification (ISO15189 Austria for medical genetics)
Personalized recipe for every person
Pellet production using your high quality natural vitamins and minerals
Shipment logistics for every order
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
Important aspects toconsider
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
TO CONSIDER
Are these tests not medical genetic tests
One important aspect of nutrigenetic tests The same test can be medical (ifdisease information is communicated) or a lifestyle test (if it onlycommunicates nutrition advice)
PPARG
Increases yourrisk of Diabetes
by 38
Makes you fatsensitive for
obesity
LIFESTYLE MEDICAL
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
TO CONSIDER
Lifestyle Genetic tests can be offered without limitations Medical genetictests are limited to qualified physicians
LCT
You are 95 likely to developlactose intolerance during
your lifetime
You need morecalcium because
of your genes
LIFESTYLE MEDICALLactose intolerance
Are these tests not medical genetic tests
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
TO CONSIDER
Another example
LCT
Your risk of osteoporosis is215 higher
You need morecalcium because
of your genes
LIFESTYLE MEDICALOsteoporosis
Are these tests not medical genetic tests
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
TO CONSIDER
Another example
GSTM1
Your risk of cancer is 130 higher due to bad
detoxification
You need more antioxidantsbecause of your genes
LIFESTYLE MEDICALDetoxification
Are these tests not medical genetic tests
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
TO CONSIDER
Another example
APOA1
Omega 3 improves your HDL cholesterol
(might be ok to communicate)
You need Omega 3 for hearthealth
LIFESTYLE MEDICALOMEGA 3
Are these tests not medical genetic tests
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
What about the science
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A1 (APOA1)
Genetic Variant rs670 GA pos -75 PromoterDisease risk Effect of poly unsaturated fatty acid consumption on HDL (good) cholesterolLow risk genotypes AA or AG show high HDL cholesterol levelsHigh risk genotypes GG shows low HDL cholesterol levels
The human Apolipoprotein A1 (APOA1) constitutes the major protein component of HDL (high-density lipoprotein the socalled ldquogood cholesterolrdquo) in plasma It promotes cholesterol efflux from tissues to the liver for excretion and is a cofactor for LCAT (lecithin cholesterol-acyltransferase) which is responsible for the formation of most plasma cholesteryl esters
A relatively frequent promoter polymorphism (GA pos -75) in the human APOA1 gene modulates the transcription of the gene as shown in a series of in vitro experiments Because low APOA1HDL plasma levels constitute a well-known risk factor for coronary artery disease (CAD) scientists started to analyze and associate this polymorphism with plasma APOA1HDL concentrations Studies that examined this association reported contradictory resultsAs a consequence it was suggested that the inconsistencies between studies could be the result of interactions with environmental factors that modulate the effect of this polymorphism Ordovas et al (2002) studied this proposed interaction in a population-based sample (755 men and 822 women) from the Framingham Offspring Study and found out that polyunsaturated fatty acids (PUFA) intake significantly modulates the effect of the APOA1 GA pos -75 polymorphism In summary in female carriers of the A-allele higher PUFA intakes were associated with higher HDL-cholesterol concentrations whereas the opposite effect was observed in GG women Their results illustrate the complexity of polymorphism-phenotype associations and underscore the importance of accounting for interactions between genes and environmental factors in population genetic studies Subbiah MT (2007) wrote in a recent review on Nutrigenetics ldquoFrom a dietary recommendation point of view women with this mutation (A-allele carriers) should be counseled to consume higher levels of polyunsaturated fatrdquoAccording to the current embodiment a person carrying the genotype GG for the rs670 genetic variant does not benefit from a high PUFA diet in terms of HDL cholesterol levels PUFAS should not be a part of nutritional supplements in this case
REFERENCESAngotti E et al 1994 PMID 8021234Juo SH et al 1999 PMID 10215547Ordovas JM et al 2002 PMID 11756058Ordovas JM 2004 PMID 15070444Subbiah MT 2007 PMID 17240315Tuteja R et al 1992 PMID 1618307
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
SCIENCE
Scientific background on the genes mentioned
GENE CADHERIN 13 (CDH13)
Genetic Variant rs8055236Disease risk Cardiovascular diseaseLow risk genotypes AA (OR 1)High risk genotypes AG (OR191) and GG (OR 223)
The present variant describes a substitution from the genetic base A to the base G at the genetic location of the CDH 13 gene The CDH13 gene encodes a member of the cadherin superfamily The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety rather than by a transmembrane domain The protein lacks the cytoplasmic domain characteristic of other cadherins and so is not thought to be a cell-cell adhesion glycoprotein This protein acts as a negative regulator of axon growth during neural differentiation It also protects vascular endothelial cells from apoptosis due to oxidative stress and is associated with resistance to atherosclerosis
The Wellcome trust Case control Consortium demonstrated in 2007 on a study of 14000 cases of seven common diseases and 3000 shared controls that the risk of cardiovascular disease of a person is increased to an odds ratio of 191 in AG heterozygotes and an odds ratio of 223 for homozygous mutants of this genetic variant when compared to the AA wildtype (The welcome Trust Case Consortium 2007) This genetic link between this genetic variant and cardiovascular disease was further demonstrated by Yan Y in 2009 in the Framingham Heart Study Offspring Cohort
Genetic evaluation According to the current embodiment a person carrying the genotypes AG or GG for the rs8055236 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsYan Y (2009) BMC Proc 2009 Dec 153 Suppl 7S118 Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study OffspringCohort Yan Y Hu Y North KE Franceschini N Lin D
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
SCIENCE
Scientific background on the genes mentioned
GENE CORONARY HEART DISEASE SUSCEPTIBILITY TO 8 (CHDS8)
Genetic Variant rs1333049Disease risk coronary heart diseaseLow risk genotypes GG (OR 1)High risk genotypesGC and CC
Two of the most frequently and thoroughly studied genetic variants for coronary heart disease susceptibility are SNPs rs10757278 and rs1333049 These two SNPs are in strong linkage disequilibrium (LD meaning that testing one completely predicts the states of the other genetic variant) and are practically ldquoequivalentrdquo In view of this strong LD specific risk evaluation can be done by only genotyping rs1333049
First identified in a study of the Wellcome Trust Case Control Consortium (2007 approx 2000 cases and 3000 controls) the rs1333049 SNP was associated with CAD having an OR of 147 and 190 for hetero- and homozygotes respectively Additional large studies could replicate this finding A meta-analysis confirmed again the association of rs1333049 with CAD in 12004 cases and 28949 controls with an OR of 124 per allele In the analysis of Schunkert et al (2008) there was no interaction concerning the risk of CAD between rs1333049 and numerous traditional risk factors including history of MI the population attributable risk (PAR) was 22 Furthermore Samani NJ et al (2007) demonstrated that in their model the prediction of MI on the basis of the FraminghamPROCAM score was improved by using the rs1333049 genotyping information
The association of this locus with CAD was also confirmed with the equivalent rs10757278 by Helgadottir A et al (2007) in a total of 4587 cases and 12767 controls all of European origin The association of the G-allele of rs10757278 with CAD was highly significant resulting in an OR of 126-128 for heterozygotes and 164 for homozygotes according to an autosomaladditive model This effect was even more pronounced in case of early-onset (menle50 years womenle60 years) myocardial infarction (MI) with an OR of 149 and 202 respectivelyAccording to the current embodiment a person carrying the genotypes GC or CC for the rs1333049 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESThe Wellcome Trust Case Control Consortium (2007) Nature 2007 June 7 447(7145) 661ndash678 Genome-wide association study of 14000 cases of seven common diseases and 3000 shared controlsHelgadottir A et al 2008 PMID 18176561Helgadottir A et al 2007 PMID 17478679
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
SCIENCE
Scientific background on the genes mentioned
GENE APOLIPOPROTEIN A5 (APOA5)
Genetic Variant rs662799Disease risk Cardiovascular disease and hypertriglyceridemiaLow risk genotypes TT (OR 1)High risk genotypes TC (OR 198) or CC (OR198)
Apoliporotein A-V (A5) is an important regulator of several lipoprotein fractions including plasma triglyceride (TG) and HDLcholesterol The mature APOA5 protein is expressed in the liver only and secreted into the plasma One of the most frequently studied polymorphism of the APOA5 gene is -1131 TC (located in the promoter region) The genotype frequency of ndash 1131 TC differs between populations The MAF (Minor Allele Frequency) of the C-allele is asymp 30 in Japanese while only asymp 12-15 in Caucasians The variant - 1131 C-allele is associated with significantly higher plasma triglyceride in multiple populations (Japan USA Germany Hungary UK etc) and in several cases with significantly decreased HDL-cholesterol concentrations Both are basic characteristics of the Metabolic Syndrome (MS) and are established risk factors for Cardiovascular Disease (CVD)
Yamada et al (2007) reported in 1788 subjects that the -1131 C- allele was significantly associated (OR=157) with Metabolic Syndrome according to a dominant model plasma triglyceride were significantly higher and HDL lower than in TT carriers In a study performed by Maaacutesz et al (2007) the 1131 C- allele ndash was again significantly associated with the Metabolic Syndrome with higher plasma triglyceride and lower HDL- concentrations Most of the studies however yielded only significant associations of ndash1131 TC variant with higher triglyceride levels and in several fewer cases with lower HDL
Szalai et al (2004) investigated the possible association of ndash1131 TC polymorphism with Coronary Artery Disease (CAD) in 308 patients referred to coronary bypass surgery and in 310 controls The prevalence of ndash1131 C-allele was significantly higher in CAD patients 109 against 57 (p lt 0001) After multiple adjustment OR=198 for developing CAD in risk-allele carriers
Vaessen et al (2006) investigated the relationship between APOA5Triglyceride and CAD in a nested case-control the Epic-Norfolk Population Study (n= 1034 cases 2031 controls) The minor ndash1131 C-allele was significantly associated with higher triglyceride concentrations and its frequency was higher in CAD casesAccording to the current embodiment a person carrying the genotypes TC or CC for the rs662799 genetic variant are considered to be at an increased risk of cardiovascular disease
REFERENCESYamada Y et al 2007 PMID 16806226Maaacutesz A et al 2007 PMID 17922054Szalai C et al 2004 PMID 15177130Vaessen SF et al 2006 PMID 16769999
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
SCIENCE
Scientific background on the genes mentioned
GENE QUINONE ACCEPTOR OXIDOREDUCTASE 1 (NQO1)
Genetic variant rs1800566 Pro187SerDisease risk Reduced conversion of Coenzyme Q10 to ubiquinol and increased oxidative stressHigh enzyme activity genotypes CC Low enzyme activity genotypes CT or TT
NAD(P)H dehydrogenase [quinone] 1 is an enzyme that in humans is encoded by the NQO1 gene This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase This FAD-binding protein forms homodimers and reduces quinones to hydroquinones Coenzyme Q10 is an oil-soluble vitamin-like substance and present in most eukaryotic cells primarily in the mitochondria It is a component ofthe electron transport chain and participates in aerobic cellular respiration generating energy in the form of ATP Ninety-five percent of thehuman bodyrsquos energy is generated this way Therefore those organs with the highest energy requirementsmdashsuch as the heart liver andkidneymdashhave the highest CoQ10 concentrations There are three redox states of coenzyme Q10 fully oxidized (ubiquinone) semiquinone(ubisemiquinone) and fully reduced (ubiquinol) The capacity of this molecule to exist in a completely oxidized form and a completely reducedform enables it to perform its functions in the electron transport chain and as an antioxidant respectively
In order for Coenzyme Q10 to act as an antioxidant the molecule needs to be converted to Ubiquinol and this transition is performed by the NQO1 enzyme The genetic variant rs1800566 produces a completely inactive enzyme and the conversion of Coenzyme Q10 is significantly slowed Therefore supplementation of Coenzyme Q10 has no beneficial health effect in carriers of the homozygous polymorphismAccording to the current embodiment a person carrying the genotype CT is considered to be an intermediate metabolizer of Coenzyme Q10 and a person carrying the TT genotype is considered to be a poor metabolizer of Coenzyme Q10
REFERENCESPMID 9271353 PMID 16551570PMID 10208650Aberg F EL Appelkvist G Dallner and L Ernster Distribution and redox state of ubiquinones in rat and human tissues Arch Biochem Biophys 295 (2) 230ndash4 1992Alleva R M Tomasetti M Battino et al The roles of coenzyme Q10 and vitamin E on the peroxidation of human low density lipoprotein subfractions Proc Natl Acad Sci 92(20)9388-91 1995Bentinger M M Tekle G Dallner Coenzyme Q ndash biosynthesis and functions Biochem Biophys Res Commun 396(1)74-79 2010Bhagavan HN and RK Chopra Coenzyme Q10 Absorption tissue uptake metabolism and pharmacokinetics Free Radical Research 40 (5) 445ndash53 2006
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
OVERVIEW
And many morehellip
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
TOUR OF THE LAB
A short tour of ourfacilities
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Novogenia reception area
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
DNA extraction laboratory
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
DNA extraction laboratory
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
storage rack for swabs currently being processed
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
DNA analysis laboratory
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
meeting room and video conferencing station
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
meeting room and video conferencing station
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
head office
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Dr Daniel WallerstorferFounder and CEO
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Sandra at the recetion desk
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Maria at the reception desk
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Saskia bringing new samples for analysis
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
paper forms are photographed and digitalized
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
we write our own software
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
presentations and trainings held via Skype
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Florian at the sample processing queue
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Saskia and Michael planning processes at the board
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Thomas sterilizing his hands
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Daniel picking up swabs to be processed
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Jenny at our DNA extraction robot 1
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Saskia checking the validity of barcoded swabs
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Florian preparing DNA extraction
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
swabs are scanned and registered in the system
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
one swab goes into one slot in a 96 well plate
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
the swabs are trimmed
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
a full plate of swabs is moved to the DNA extraction robot
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
192 swabs are extracted in 15h
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
DNA is the transferred into a DNA plate
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
DNA extraction is fully automated
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
we have 3 large DNA extraction robots
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
and 2 small DNA extractors
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
total extraction capacity 100 000 swabs per month
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
we use high capacity 384 well plates
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
these can analyze 72 samples at once
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
mixing DNA with reagents is also automated
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
plates are cooled during preparation for analysis
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Daniel preparing a liquid handling robot
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Robots use filter tips to avoid contamination
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Reagents are prepared in UV sterilized cabinets
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
Maria preparing the analysis process
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
the Viia7 is the most advanced DNA analyzer
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
the machine can analyze 384 genes in 1h
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
adding up to 720 samples per 10h day
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
we operate a loading robot for 247 operation
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
the robot removes completed plates and loads new ones
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
plates are barcode labeled and automatically recorded
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
total analysis capacity is 51 000 samples per month
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
every bay holds 45 plates or 3200 customers
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
our alternative DNA analyzer in ring-format
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
office area ndash we are largely paper less
opened swabs are sprayed with DNA degrading chemicals
opened swabs are sprayed with DNA degrading chemicals
