Ahmed El-Sohemy Department of Nutritional Sciences University of Toronto Coffee, Caffeine and...
-
Upload
alexa-hutchinson -
Category
Documents
-
view
214 -
download
0
Transcript of Ahmed El-Sohemy Department of Nutritional Sciences University of Toronto Coffee, Caffeine and...
Ahmed El-Sohemy
Department of Nutritional SciencesUniversity of Toronto
Coffee, Caffeine and Cardiovascular Disease
Canada Research Chair in Nutrigenomics
Diet Genes
Nutrigenomics:
Using genomic information and techniques inmolecular genetics & genomics to address issues important to nutrition and health.
Food preferences
Confounding (residual)
Measurement error
Recall Bias (case-control)
Why bother with genetics/genomics?
Challenges for Nutritional Epidemiology
Coffee or associated lifestyle?
Are coffee abstainers at risk?
Does risk depend on age?
Which component of coffee?
Is Coffee associated with CVD?
magnesium
potassium
polyphenols
caffeine
aliphatic acids
diterpenoids
melanoidins
caffeine
Bioactives in coffee
Caffeine
CYP1A2
1-methylxanthine
1-methyluric acid
5-acetylamino-6-formylamino-3-methyluracil
1,7-dimethyluric acid
Paraxanthine
CYP1A2 Genotype
A/A A/C C/C
% In
duci
bilit
y
0
50
100
150
200
250
300
Genetic Variation in CYP1A2 -163 AC
slow
fast
Costa Rica Study
• 2013 cases (myocardial infarction)• 2013 population-based controls
- matched (age, sex, area of residence)
• Data collection: - food frequency questionnaire - health and lifestyle questionnaire - fasting blood sample (DNA)
CYP1A2 Genotype Distribution
slow
rapid
CYP1A2
Genotype
Controls
%
Cases
%
A/A
A/C
C/C
46
43
10
45
44
11
Total Population
Od
ds
Ra
tio
0.5
1.0
1.5
2.0
<1 cup/d1 cup/d2-3 cups/d4+ cups/d *
* P<0.05
Coffee Intake and Risk of Myocardial Infarction
Cornelis et al., JAMA 295: 1135-41, 2006
CYP1A2 Genotype
*1A/*1A *1A/*1F + *1F/*1F
Od
ds
Rat
io
0.5
1.0
1.5
2.0
<1 cup/d1 cup/d2-3 cups/d4+ cups/d
A/A A/C + C/C
* P<0.05
*
*
Cornelis et al., JAMA 295: 1135-41, 2006
Coffee Intake and Risk of Myocardial Infarction
CYP1A2 Genotype
*1A/*1A *1A/*1F + *1F/*1F
Od
ds
Rat
io
0
1
2
3
4
<1 cup/d1 cup/d2-3 cups/d4+ cups/d
A/A A/C + C/C
Subjects <50 Years of Age
Coffee Intake and Risk of Myocardial Infarction
* P<0.05
*
*
*
*
Cornelis et al., JAMA 295: 1135-41, 2006
Adults 10-12 y 7-9 y 4-6 y
Caf
fein
e m
g/d
0
100
200
300
400
500
Pregnant & Nursing
Recommended Maximum Caffeine Intake(Health Canada)
Caffeine
Polyphenols
Diterpenes
ADR ADORAHTT GRKHTR COMT
CETP PLTPLDLR ACATSREBP GST
ACE TNFNFB VCAM1PKC PPARGPDE CREBGLUT PKA
GLP1R GLUTFAS1 ACENOX G6PT1
Genetic modifiersof exposure
Genetic modifiersof biological effect
CHDRisk
Flavonoids
CYP1A2 FMOCYP2A6 NAT2CYP2E1
UGTSULT
CYP1A2 CYP3A4CYP2D6 CYP1A1 UGT SULTCYP2C9 CYP2E1
UGTGSTSULT
Curr. Opin. Lipidol, 18: 13-19, 2007
Caffeine Consumption Habits Study
• Healthy Men and Women aged 20-29 years (n=940)
• Food Frequency Questionnaire
- Caffeine consumption
• Caffeine Consumption Habits Questionnaire - Acute effects of caffeine
- Caffeine withdrawal symptoms - Limiting or avoiding caffeine
Sex
Men Women
% R
epo
rtin
g E
leva
ted
Mo
od
0
10
20
30
40
50
60
70 C/CC/TT/T
* P<0.05
**
*
** P<0.005
DRD2 C957T Genotype and “Elevated Mood” Among Men and Women
Sex
Men Women
Fre
qu
ency
of
TT
Gen
oty
pe
(%)
0
5
10
15
20
25 < 50 mg/d50-200 mg/d> 200 mg/d
* P<0.05
*
DRD2 C957T Genotype and Caffeine Intake Among Men and Women
ACKNOWLEDGMENTS
Marilyn Cornelis Leah CahillKaren Eny Bénédicte Fontaine-Bisson Ilana PlattStephen OzsungurClare Toguri
Canada Research Chairs
Canadian Institutes of Health Research
Natural Sciences and Engineering Research Council
Advanced Foods and Materials Network Centres of Excellence
Hyeon-Joo LeeLindsay Stewart Daiva NielsenAlejandra Navarro-Allende Susana HuangSarah HerdDarren BrennerBibiana Garcia-Bailo
Hannia Campos Edmond KabagambeTom WoleverCCD InvestigatorsPaul CoreyDavid Jenkins