Genetic markers for insulin-dependent diabetes mellitus in Japanese.

Although the HLA class II genes are clearly associated with insulin-dependent diabetes mellitus (IDDM) in all ethnic groups, considerable variation in the associated haplotypes is observed among the ethnic groups. In Japanese, DRB1*0405-DQA1*0301-DQB1*0401, DRB1*0901-DQA1*0301-DQB1*0303 and DRB1*0802-DQA1*0301-DQB1*0302 are the major susceptibility haplotypes to IDDM, while DRB1*1501-DQA1*0102-DQB1*0602 and DRB1*1502-DQA1*0103-DQB1*0601 are the major resistance haplotypes. The hypothesis that alleles encoding amino acids other than aspartic acid at the DQB1 position 57 contribute to IDDM susceptibility is not applicable to the Japanese, mainly because the first and second susceptibility haplotypes listed above have aspartic acid at DQB1 position 57. In the 5' insulin gene polymorphism, the shorter insertion (class 1 allele) is predominant, and is not associated with diabetes in Japanese. Subdivision of the class 1 alleles also failed to show an association with IDDM in Japanese. The insulin gene region appeared to be of less value as a genetic marker for IDDM in Japanese. Little is known about other genetic markers.