K. Yamada et al., CODON-972 POLYMORPHISM OF THE INSULIN-RECEPTOR SUBSTRATE-1 GENE IN IMPAIRED GLUCOSE-TOLERANCE AND LATE-ONSET NIDDM, Diabetes care, 21(5), 1998, pp. 753-756
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.