Peroxisome proliferator-activated receptor y2 Pro115Gln and G972R insulin substrate receptor-1 variants in obesity and insulin resistance

ABSTRACT

Objective: The association among IRS-IG972R and PPAR-gama2Pro1l5Gln gene variants and insulin resistance is controversial. This study aimed to investigate the relationship between PPAR-gama2Pro115Gln and IRS-IG972R variants to in­sulin resistance. Design and Setting: This prospective study was developed in the University Hospital of Unicamp. Methods: We studied the prevalence of these mutations in 67 lean and 64 obese subjects (91 women and 40 men, 18 to 67 years old) evaluating metabolic and obesity parameters. Both genetic variants were detected by restriction fragment length polymorphism assays. Insulin sensitivity was estimated through the insulin resistance index; Body Mass Index (BMI), waist, fat and fat-free mass, indirect calorimetry, blood pressure, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting plasma glucose, insulin and serum uric acid were also measured. Results: Genetic analysis showed that 5 (3.8%) individuals presented mutations in the PPAR-gama2 gene, all of them homozygotes, whereas polymorphism of the IRS-l gene was found in 12 (9.1 %) cases, all in heterozygosis. There was no correla­tion between the genetic profile and insulin resistance or any ofthe anthropometric, hemodynamic and biochemical parame­ters measured in the obese group. The rate of PPAR-gama2 and IRS-l variants was similar in lean and obese subjects. Among the PPAR-gama2Pro1l5Gln carriers, 3 were insulin resistant (p equal 0.05 HOMA-IR greater that 75th). Conclusion: We suggest that there is a trend to the asso­ciation between the PPAR -gama2Pro 115, but not the IRS-l G972R gene mutation to insulin resistance in the Brazilian population, that needs to be confirmed in larger samples.