Analysis of codon 972 (Gly → Arg) polymorphism in IRS-1 gene in type 2 diabetic population

Abstract

Polymorphism of Insulin Receptor Substrate-1, especially the GGG→AGG (Gly-Arg) substitution at codon 972, is one of the major factors leading to the development of type 2 diabetes mellitus. This defect in IRS-1 causes insulin resistance along with many other consequences. It generally impairs insulin signalling via the phosphadylinositol-3 (PI3)-Kinase pathway. In this study, the heterozygous Gly→Arg substitution at codon 972 of the IRS-1 gene was found in 2 of the 43 control Indian subjects, which is higher than normal when compared with the other population. The prevalence of the codon 972 GGG→AGG substitutions was found to be around 4.6%, which may be due to a predisposition factor. In diabetic subjects, on the other hand, 5 out of 43 showed substitution at codon 972, with a percent prevalence of 14%, establishing the role of the polymorphism of IRS-1 codon in the prevalence of diabetes mellitus.