Association Study of IRS1 Gene Polymorphisms with Type 2 Diabetes in South Indians

Background and Objectives: The insulin receptor substrate-1 (IRS1) gene is a candidate gene for type 2 diabetes. The aim of this study was to investigate the association of the IRS1 gene polymorphisms Gly972Arg and Ala513Pro with type 2 diabetes in an Asian Indian population in south India. Methods: A total of 2,148 subjects (1,187 normal glucose-tolerant [ NGT] and 961 type 2 diabetes subjects) were randomly selected from the Chennai Urban Rural Epidemiology Study. The IRS1 gene polymorphisms Gly972Arg and Ala513Pro were genotyped in these subjects using polymerase chain reaction-restriction fragment length polymorphism, and a few variants were confirmed by direct sequencing. Results: The frequency of the A allele of the Gly972Arg(G -> A) single nucleotide polymorphism was similar between the NGT and diabetes subjects (2%). There was no significant difference in the genotypic frequency between the NGT and type 2 diabetes group (P = 0.25). When the study subjects were stratified based on body mass index (BMI) as per World Health Organization Asia Pacific guidelines as nonobese (BMI < 25 kg/m(2)) and obese (BMI >= 25 kg/m(2)), neither the allelic frequency (nonobese, P = 0.44; obese, P = 0.37) nor the genotypic frequency (nonobese, P = 0.29; obese, P = 0.35) was significantly different between the NGT and type 2 diabetes groups. The Ala513Pro polymorphism was first genotyped in 500 NGT and 500 type 2 diabetes subjects. None of these subjects carried the Ala513Pro or the Pro513Pro genotype. Hence, the Ala513Pro polymorphism was not genotyped further. Conclusion: The IRS1 gene variants Gly972Arg and Ala513Pro are not associated with type 2 diabetes in this south Indian population.