[The influence of polymorphism the Gly972Arg variant insulin receptor substrate-1 (IRS-1) gene, and G-308A TNF-alpha gene on obesity and insulin resistance in children with obesity].
Genetic factors play a role in the pathogenesis of insulin resistance in obese subjects. The insulin receptor substrate-1 (IRS-1) and IRS-2 are the most important elements of the insulin-signaling pathways, and mutations in this gene have been reported to play a role in determining insulin resistance, particulary in presence of obesity. The polymorpism of the TNF-a-308 gene is also involved in the development of obesity-related insulin resistance, therefore, we investigated whether the IRS-1 and TNF-a polymorphism can predict conversion to insulin resistance and obesity parameters in children with obesity.


METHODS
The 70 children with obesity simplex were included in this study (9-18 y.o). The antropometric investigations: weight, height, BMI, SDS for BMI, WHR, sum of 3, 10 skinfolds, and percent of body fat by Slaughter's equation was calculated. In each children after 12 hour overnight fast glucose, insulin, leptin and lipids: triglycerides (Tg), cholesterol total (Chol-T), cholesterol HDL (Chol-HDL), cholesterol LDL (Chol-LDL) were measured. The oral glucose tolerance test was performed and HOMA-IR was calculated.


RESULTS
Two variants of genotypic IRS-1 were obtained: C/C(85.7 %), A/C(14.3%), and 3 variants of TNF-a G/G 68 % A/G 29% A/A 3%. Statistical analysis of anthropometric and biochemical variables in groups C/C, vs A/C and variables between IRS and TNF (G/G, A/G + A/A) groups was performed. We did not find any significant differences between these groups in the t-Student test. The girls heterozygous for the A allele--A/C (IRS) had higher body weight than girls who were homozygous C/C (chi(2) =3.87, Pr>chi(2)=0,048). In smaller children studies, both polymorphism--IRS and TNF seems not to be associated with the degree of obesity and insulin resistance.
Pyrzak
Beata
B
Katedra i Klinika Pediatrii and Endokrynologii AM w Warszawie, Warszawa. endokrynologia@litewska.edu.pl
Wiśniewska
Alicja
A
Rymkiewicz-Kluczyńska
Barbara
B
D000293:Adolescent; D001120:Arginine / Q000235:genetics; D002648:Child; D005260:Female; D005787:Gene Frequency; D005998:Glycine / Q000235:genetics; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008297:Male; D009765:Obesity / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011972:Receptor, Insulin / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D008055:Lipids; D010750:Phosphoproteins; D014409:Tumor Necrosis Factor-alpha; D001120:Arginine; D011972:Receptor, Insulin; D005998:Glycine