Diabetes Care, Vol 21, Issue 5 753-756, Copyright © 1998 by American Diabetes Association

ARTICLES

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

K Yamada, X Yuan, S Ishiyama, S Shoji, S Kohno, K Koyama, A Koyanagi, W Koyama and K Nonaka
Department of Medicine, Kurume University School of Medicine, Kurume, Japan. yamada@med.kurume-u.ac.jp

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: The codon 972 variant may be associated with IGT and a subset of late-onset NIDDM in the elderly Japanese population.
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