Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma 2 (PPAR gamma-2) gene is associated with greater insulin sensitivity and decreased risk of type 2 diabetes in an Iranian population

Background: The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma 2 (PPAR gamma-2) gene has been variably associated with insulin resistance, obesity and type 2 diabetes in several populations. However, this association has not been studied in Iranian subjects and we hypothesized that this variation might be associated with insulin resistance, type 2 diabetes and related metabolic traits in this population. Methods: The Pro12Ala genotypes were determined by PCR-restriction fragment length polymorpism in 696 unrelated subjects including 412 non-diabetic controls and 284 type 2 diabetic patients. Results: The frequency of the Ala allele was 9.4% and 5.9% in controls and type 2 diabetic subjects, respectively [adjusted odds ratio (OR) 0.457, p=0.005]. The Ala allele did not show a significant effect on anthropometric and biochemical parameters in the type 2 diabetic group, whereas in non-diabetic subjects, carriers of the Ala allele had significantly lower fasting insulin (p=0.007) and homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.009) levels compared to Pro/Pro subjects. Multivariate logistic regression analysis showed that Pro12Ala polymorphism was an independent determinant of type 2 diabetes in this population. Conclusions: Our results for a sample of Iranian type 2 diabetes cases and controls provide evidence that the Pro/Ala genotype of the PPAR gamma-2 gene is associated with insulin sensitivity and may also have protective role against type 2 diabetes.