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Association study of IRS1 gene polymorphisms with type 2 diabetes in south Indians
Dhanasekaran Bodhini1, Venkatesan Radha, Viswanathan Mohan
1Madras Diabetes Research Foundation, ICMR Advanced Centre for Genomics of Type 2 Diabetes, Chennai, India.
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.
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