AMINO-ACID POLYMORPHISMS OF THE INSULIN-RECEPTOR SUBSTRATE-1 IN JAPANESE NONINSULIN-DEPENDENT DIABETES-MELLITUS

By using polymerase chain reaction-restriction length polymorphism and polymerase chain reaction-single-strand conformation polymorphism ana lysis, we screened 283 Japanese subjects [226 noninsulin-dependent dia betes mellitus (NIDDM), 12 impaired glucose tolerance, and 45 normal c ontrols] for 2 amino acid polymorphisms, Ala513Pro and Gly972Arg, of t he insulin receptor substrate-1. Only 8 NIDDM, 1 impaired glucose tole rance, and 1 normal subject were identified to be heterozygous for the Gly972Arg mutation, whereas no subject had an Ala513Pro polymorphism. The frequency of Gly972Arg was lower than recently reported in Danish and Finnish populations and was in goad agreement with that previousl y reported in another Japanese cohort. Analysis of I pedigree of 1 NID DM patient with a Gly972Arg showed no co-segregation between this poly morphism and the onset of NIDDM. Our results suggest that the Gly972Ar g polymorphism does not play an important role in the pathogenesis of NIDDM in Japanese patients.