PPAR-72 Pro12Ala polymorphism is associated with post-challenge abnormalities of glucose homeostasis in children and adolescents with obesity

摘要

Aim: The aim of the study was to investigate the association between PPAR-72 Prol2Ala polymorphism and laboratory characteristics of carbohydrate metabolism in children and adolescents with obesity. In addition, serum levels of tumor necrosis factor (TNF)-alpha, and soluble form of its receptors (sTNFRl and sTNFR2) were assessed. Methods: In a cross-sectional study, 79 obese children and adolescents of Caucasian origin were investigated. PPAR-gamma2 Pro 12Ala polymorphism was determined using polymerase chain reaction - restriction fragment length polymorphism technique. Serum levels of TNF-alpha, sTNFRl and sTNFR2 were measured by enzyme amplified sensitivity immunoassay. Results: The minor Ala allele frequency was found to be 14.56% in our cohort. No significant differences in age, BMI, waist circumference, blood pressure, serum lipid, uric acid, TNF-a, sTNFRl and sTNFR2 values were found between carriers of the Ala allele (Pro/Ala and Ala/Ala; n=21) vs. homozygous carriers of the Pro allele (Pro/Pro; n=58). However, post-challenge (120 min) plasma glucose and insulin values were significantly lower in Ala allele carriers vs. homozygous Pro allele carriers (6.56+0.26 vs. 7.36+0.25 mmol/L and 65.9+13.8 vs. 111.8+-20.7 muU/mL, respectively; p<0.05); while no significant differences were found at fasting state.Conclusions: The association between PPAR-gamma2 Prol2Ala polymorphism and glucose metabolism is already present in children and adolescents with obesity who might be at the very beginning of the natural course of type 2 diabetes. At this stage, higher insulin sensitivity can be detected in Ala allele carriers compared to homozygous Pro subjects at post-challenge but not in fasting state; however, the TNF-system seems not to be involved in the alteration of glucose homeostasis due to PPAR-gamma2 Prol2Ala polymorphism.