The Relation of Interleukin 6 Gene-190 T/C Polymorphisms with Anthropometric and Biochemical

Characteristics in a group of Obese Children

Authors: Mărginean Maria Oana, Tripon Florin

Coordinators: Bănescu Claudia, Pitea Ana Maria

Introduction

• Genetic variability of the IL-6-190 gene in humans-allele T or C

• Asociated with other hereditary diseases– Including nutritional disorders

• malnutrition• obesity

Introduction

• Obesity– represents a problem with great importance and certain

actuality in the field of pediatric pathology because of its increased incidence in children and its complications (cardiovascular, metabolic, renal)

– Excessive or abnormal accumulation of fat in the adipose tissue

– Recent data suggests that obesity

• may have an inflammatory etiology

• asociates a low-degree proinflammatory status

Background

• Pathogenesis

– genetic factors

– environmental factors

• diet – excesive intake

• decrease in physical activity

– psycho-emotional factors

– stress

Introduction

• the adipocyte:– secretes hormones, growth factors, cytokines

(proinflammatory)

– receptors for hormones, cathecolamines, prostaglandines

– influences the energetic metabolism

Introduction

• the adipocyte stocks cytokines (IL6, TNFα)

• The cytokine level (IL) was bigger in the supraponderal and obese children, in comparison with the normoponderal group

– positively corelated with the antropometric indexes

– and with different complications

IL-6• IL-6 - an inflammatory cytokine involved in the regulation of energy

balance

• IL-6 regulates the acute phase response and inflammation, which influence the function of adipose tissue, the levels of IL6 being increased in obese patients and with cardiovascular diseases

• IL-6 deficit - associated with obesity, hypofunction of T cells, and neuroendocrine/ metabolic dysfunction

• the C allele has been associated with a risk of high blood pressure and of coronary disease.

• studies reported a positive correlation between TNF-ɑ, IL-6, the level of leptin, the mass of adipose tissue and BMI

• possible marker of obesity complications

the IL-6 gene 190 T/C polymorphism influences the producing and plasma-level of this cytokine

Objective

• the study of clinical and genetic factors in children with obesity

• I examined if the obese patients are different concerning the IL-6 – 190 genotypes

• and also the correlation of this genotype with

– anthropometric and

– biochemical parameters

Material and methods• 182 children divided in 2 comparable age and

gender groups– admitted in Pediatrics Clinic I

– in the period October 2012 – March 2014

• 86 with obesity • 96 with normal weight/ control group

• the following were evaluated:– anthropometric parameters

– biochemical metabolism parameters

– cytokine levels

Material and methods• anthropometric parameters

• BMI, body mass index

• medium upper-arm circumference / MUAC

• Tricipital skinfold/ TSF

– biochemical metabolism parameters• proteins, lipidic prophile, albumins

– IL-6 190 T/C polymorphism analysis (using specific primers).

Material and methods• Including criteria in the study

– control group – healthy pediatrics patients– obese children

• children and adolescents with obesity• children with increased weight, BMI, MUAC and TSF

• excluding criteria: – Children and adolescents with genetic diseases– Metabolic disorders that could influence the weight– Other chronic diseases that could influence the nutritional

status

• Statistical calculation

– For the entire statistical calculation

• Graph Pad 3.6 Software, San Diego, California, United Stated of Smerica

– For the evaluation of the normality of continuous variables (for example IMC, MUAC, TST, etc)

• I applied the t-Student test

• Expressing the anthropometric parameters measured as standard deviations (Z score) and calculation of some correlative indexes

Material and methods

Results

• the medium age of the children included in the study

– 9.67 ± 3.52 years in control group

– 9.21± 2.11 years in obese group

• without significant statistical difference between the two groups

Results – anthropometry

ParameterControlN=86

ObeseN=96

p

BMI z (median-range) -0.04 (-1,54-1.9) 2.81 (2-7.18) 0.0001

MUAC z (median-

range)-0.26 (-5.5-7.8) 4.8 (-1.3-13.9) 0.0001

TST z (median-range) -0.9 (-5.9-9.41) 2.91 (-1.3-8.65) 0.0001

Proteins obese vs. control

T chol obese vs. control

Results - biochemistry

Parameter

ControlN=86

ObeseN=96

p

Glicemya 84,7 ± 3,43 99.67 ± 2,13 0,08

Proteins 7.2 ± 0.55 8.1± 0.53 0,04

Total Chol

146 ± 23.48

162.17 ± 14.64 <0.05

Glicemya obese vs. control

VariablesControl group

(n = 86)

Obese

(n = 96)p value

IL-6 190

no (%)

CC 30 (34.88) 14 (14.58) 0.0001

CT 37 (43.02) 71 (73.95) 0.0001

TT 19 (22.09) 11 (11.45) 0.08

Results - polymorphisms

• The CT genotype was observed to appear more frequently in the obese group (73.95%) than in the control group (p=0.0001)

• CC homozygotes, as well as the T allele, predominated in the control group

Anthropometric and

paraclinical parameters

CC 

CT TT

control obese p value control obese p value control obese p value

MUAC# SD median (range)

-0.36(-5.3-9.1)

4.4(-1.3-6.2)

0.0001-0.25

(-2.93-9.1)4.6

(-1.12-10.1)

0.0001-0.25

(-1.9-7.5)

3.6(-1.06-

7.8)

0.0001

TST# SDmedian (range)

-0.87(-5.9-3.9)

2.13(-1.37-3.4)

0.0001 -0.06(-2.9-6.9)

3.2(0.2-8.2)

0.0001 -0.25(-3.9-9.1)

2.5(0.7-5.6)

0.0001

Total protein g/dl ##

(mean SD)7.48±0.73 7.7±0.56

 NS 7.4±0.57 7.5±0.5

 NS 7.43±0.7 7.47±0.3

 NS

Albumin# g/dl(mean SD)

4.4±0.58 4.8±0.450.0001

4.4±0.5 4.6±0.480.0001

4.28±0.42 4.68±0.370.0001

The correlations between the anthropometric and laboratory parameters and IL-6 190 genotype

Results - polymorphisms

• The polymorphism of the gene IL-6 190 T/C was correlated with anthropometric and paraclinical parameters:

MUAC and TST had statistically significantly higher values in the obese group for the IL-6 190 CC, CT and TT haplotypes (p=0.0001)

the same has been observed for albumins as biochemical parameters

Results

• we observed a very low TT percentage (11.45%) and a high percentage of the CT and CC alleles (88.53%) in the obese group

the C carriers IL6-190 increased in frequency in the obese group

• with significant p of 0.04 (OR=2.3, 95% CI=1.06–4.9)

• There are significant statistical differences between the study group and the control one regarding

– the anthropometric parameters (WHA, MUAC, TSF)

• much more higher values in the obese comparatively with the control group

– biochemical parameters

• It can be observed that the values of glycemia and cholesterol are significantly higher in children with obesity comparatively with the control group

Results

Conclusions

•C carriers IL-6 190 were increased in frequency in the obese group, with a significant p of 0.04

•CT heterozygotes were the most frequent genotypes in the obese children

•BMI, MUAC, TST, and serum albumin levels correlate with the IL-6 190 C alleles in children with obesity

•The polymorphism of the gene IL-6 190 T/C may modulate genes to determine the nutritional status and may be associated with the risk of developing obesity