Insulin resistance and glucose dysmetabolism in polycystic ovary syndrome (PCOS) are related with the polymorphisms in the genes encoding the insulin receptor substrate (IRS) proteins, especially Gly972Arg/Ala513Pro polymorphism being reported to be associated with type-2 diabetes and PCOS.
Five variant sequences of IRS-1 were identified with the NIDDM subjects; 2 silent polymorphisms at codons 235 (GGG to GGA) and 893 (CCG to CCC): 2 non-conservative mutations (Ala513Pro; Gly972Arg) and a codon deletion (Ser681-7 to Ser681-6).
Two mutations of the IRS-1 gene (Gly(972)Arg and Ala(513)Pro) have been described, although their roles in the development of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM) remain controversial.
The purpose of this study was to examine the role of the IRS-1 missense mutations at codons 972 (glycine to arginine) and 513 (alanine to proline) in two diverse populations from South India and Finland at high risk for NIDDM.
We studied a simple tandem repeat DNA polymorphism in the glycogen synthase gene and polymorphisms at codon 513 (Ala-->Pro) and 972 (Gly-->Arg) in the insulin receptor substrate-1 (IRS-1) gene in 197 non-insulin-dependent diabetes mellitus (NIDDM) and 178 control subjects in Japan.