Codon 972 polymorphism of the insulin receptor substrate-1 gene in impaired glucose tolerance and late-onset NIDDM.

Abstract

To assess the relevance of a Gly-->Arg substitution in codon 972 of the insulin receptor substrate-1 gene in impaired glucose tolerance (IGT) and NIDDM. The genotype of 1,106 Japanese subjects consisting of 310 subjects with NIDDM, 305 subjects with IGT, and 491 normal control subjects was analyzed by an allele-specific assay using polymerase chain reaction and restriction fragment length polymorphism. The frequency of the variant allele was not different between subjects with NIDDM (0.021) and normal control subjects (0.020). However, subjects with IGT showed a significantly higher prevalence of the variant allele (0.041, P = 0.027). We found two homozygous individuals for the variant; both had IGT with mild insulin resistance. The allelic frequency tended to be lower in normal control subjects aged > 50 years than in younger control subjects. Conversely, in the subjects with IGT or NIDDM, the Gly972Arg substitution was more frequently found in subjects aged > 50 years. Furthermore, NIDDM patients with the variant allele had older ages of diagnosis than patients without the variant. The codon 972 variant may be associated with IGT and a subset of late-onset NIDDM in the elderly Japanese population.