1. 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

2. 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

3. 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

4. Background Pathogenesis –genetic factors –environmental factors diet – excesive intake decrease in physical activity –psycho-emotional factors –stress

5. Introduction the adipocyte: –secretes hormones, growth factors, cytokines (proinflammatory) –receptors for hormones, cathecolamines, prostaglandines –influences the energetic metabolism

6. 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

7. 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 IL 6 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

8. 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

9. 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

10. 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).

11. 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

12. 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

13. 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

14. Results – anthropometry Parameter Control N=86 Obese N=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

15. Proteins obese vs. control T chol obese vs. control Results - biochemistry Paramete r Control N=86 Obese N=96 p Glicemya 84,7 ± 3,43 99.67 ± 2,13 0,08 Proteins7.2 ± 0.558.1± 0.530,04 Total Chol 146 ± 23.48 162.17 ± 14.64 <0.05 Glicemya obese vs. control

16. Variables Control group (n = 86) Obese (n = 96) p value IL-6 190 no (%) CC30 (34.88)14 (14.58)0.0001 CT37 (43.02)71 (73.95)0.0001 TT19 (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

17. Anthropometr ic and paraclinical parameters CC CT TT controlobesep valuecontrolobesep valuecontrolobesep 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# SD median (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±0.737.7±0.56 NS 7.4±0.577.5±0.5 NS 7.43±0.77.47±0.3 NS Albumin# g/dl (mean SD) 4.4±0.584.8±0.45 0.0001 4.4±0.54.6±0.48 0.0001 4.28±0.424.68±0.37 0.0001 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

18. 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 IL 6 -190 increased in frequency in the obese group with significant p of 0.04 (OR=2.3, 95% CI=1.06–4.9)

19. 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

20. 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