Association of Insulin Receptor Substrate-1 Gene Polymorphism with Insulin Resistance in Type 2 Diabetes Mellitus in Iraqi Population

Abstract

A glycine to arginine substitution (GGG?AGG substitutions) in codon 972   (Gly 972 Arg) is the common polymorphism of the IRS-1 gene. This polymorphism interfere with the interaction between IRS-1 and PI3-kinase. It participate in the development of insulin resistance and diabetes by impairing the ability of insulin to activate the  IRS-1/PI3-kinase/Akt signaling pathway. The present study was designed to evaluate the association of insulin receptor substrate-1 gene G?A (Gly 972 Arg) polymorphism with insulin resistance in type 2 diabetes mellitus in Iraqi population. To achieve this aim, 103 of type 2 diabetic patients and 57 apparently healthy control group were subjected to the study. The results of present study show that the heterozygous genotype (GA) of insulin receptor substrate-1 gene G?A (Gly 972 Arg) SNP was significantly increased (OR=9.14, CI 95% 1.13-75.53, P < 0.05) the risk of type 2 DM by nine folds with respect to those of wild genotype (GG). The allele frequencies of G and A were 92.93% and 7.07% for the insulin resistant type 2 diabetic patients group and 99.04% and 0.96% for the control group respectively. Also, the results revealed that no significant differences in clinical characteristics between wild genotype (GG) and heterozygous genotype (GA). The study concluded that insulin receptor substrate-1 gene G?A (Gly 972 Arg) SNP are associated and involved in the pathogenesis of  insulin resistant type 2 diabetes mellitus.

Keywords: Diabetes Mellitus, Insulin resistance, IRS-1, Gly 972 Arg