INSULIN GENE REGION CONTRIBUTES TO GENETIC SUSCEPTIBILITY TO, BUT MAYNOT TO LOW INCIDENCE OF, INSULIN-DEPENDENT DIABETES-MELLITUS IN JAPANESE

In the Caucasian population, it has been demonstrated that the insulin gene (INS) region contains the insulin-dependent diabetes mellitus lo cus (IDDM2). In the Japanese population, however, there has been no re port demonstrating the contribution of IDDM2 to the pathogenesis of ID DM. We conducted an association study of IDDM in a large number of Jap anese subjects with multiple polymorphisms in INS region. We found a s ignificant association of the INS region with IDDM. Alleles positively associated with IDDM in INS region were the same as those positively- associated with IDDM in Caucasian population, although positively-asso ciated alleles are very common (allele frequencies > 0.9) in the Japan ese general population. These data suggest that IDDM2 is involved in t he genetic susceptibility to IDDM in Japanese. The high frequencies of disease-associated alleles in the general population suggest that IDD M2 locus is not responsible for the low incidence of IDDM in Japanese. (C) 1997 Academic Press.