Insulin Gene Region Contributes to Genetic Susceptibility to, but May Not to Low Incidence of, Insulin-Dependent Diabetes Mellitus in Japanese

Abstract

In the Caucasian population, it has been demonstrated that the insulin gene (INS) region contains the insulin-dependent diabetes mellitus locus (IDDM2). In the Japanese population, however, there has been no report demonstrating the contribution ofIDDM2to the pathogenesis of IDDM. We conducted an association study of IDDM in a large number of Japanese subjects with multiple polymorphisms inINSregion. We found a significant association of theINSregion with IDDM. Alleles positively associated with IDDM inINSregion were the same as those positively-associated with IDDM in Caucasian population, although positively-associated alleles are very common (allele frequencies > 0.9) in the Japanese general population. These data suggest thatIDDM2is involved in the genetic susceptibility to IDDM in Japanese. The high frequencies of disease-associated alleles in the general population suggest thatIDDM2locus is not responsible for the low incidence of IDDM in Japanese.