CODON-972 POLYMORPHISM OF THE INSULIN-RECEPTOR SUBSTRATE-1 GENE IN IMPAIRED GLUCOSE-TOLERANCE AND LATE-ONSET NIDDM

OBJECTIVE - To assess the relevance of a Gly-->Arg substitution in cod on 972 of the insulin receptor substrate-1 gene in impaired glucose to lerance (IGT) and NIDDM. RESEARCH DESIGN AND METHODS - The genotype of 1,106 Japanese subjects consisting of 310 subjects with NIDDM, 305 su bjects with IGT, and 491 normal control subjects was analyzed by an al lele-specific assay using polymerase chain reaction and restriction fr agment length polymorphism. RESULTS - The frequency of the variant all ele was not different between subjects with NIDDM (0.021) and normal c ontrol subjects (0.020). However, subjects with IGT showed a significa ntly higher prevalence of the variant allele (0.041, P = 0.027). We fo und two homozygous individuals for the variant; both had IGT with mild insulin resistance. The allelic frequency tended to be lower in norma l control subjects aged >50 years than in younger control subjects. Co nversely, in the subjects with IGT or NIDDM, the Gly972Arg substitutio n was more frequently found in subjects aged >50 years. Furthermore, N IDDM patients with the variant allele had older ages of diagnosis than patients without the variant.CONCLUSIONS - The codon 972 variant may be associated with IGT and a subset of late-onset NIDDM in the elderly Japanese population.