HLA-DQ system and insulin-dependent diabetes mellitus in Japanese: does it contribute to the development of IDDM as it does in Caucasians?

Abstract

Fifty-six unrelated Japanese patients with insulin-dependent diabetes mellitus (IDDM) were HLA-typed, and restriction fragment length polymorphism (RFLP) analysis was performed after enzyme digestion with Bam HI and Taq I by using both DR and DQ probes. As previously reported, increased frequencies of Bw54, Cw1, DR4, and DRw53, which are in strong linkage disequilibrium in the Japanese population and make the characteristic Japanese haplotype, were confirmed. DQw4, a new allele of the DQ system recognized by the monoclonal antibody HU-46 and in linkage disequilibrium with this haplotype, presented the highest IDDM association. The RFLP analysis also showed the strongest correlation to IDDM when the DQ probe was applied. These results indicate that HLA-DQ might play the most important role in the development of IDDM in Japanese as well as in Caucasians. The correlation of DQ beta amino acid sequences strongly associated with IDDM in Japanese are discussed in this study, and contrasting results were found when such sequences were compared with those of Caucasians.

The A3 allele of the HLA-DQA1 locus is associated with susceptibility to type 1 diabetes in Japanese.

“…The results and the calculated relative risks are in close agreement with those reported previously from studies of Japanese patients and controls (23)(24)(25). Both DR4 (relative risk = 4.62; P = 0.003) and DR9 (relative risk = 2.22; P value, not significant) are increased in the patient group, whereas the frequencies of the antigens DR2 (relative risk = 0.29; P = 0.036) and DR5 (relative risk = 0.13; P = 0.017) are decreased.…”

Age-dependent HLA genetic heterogeneity of type 1 insulin-dependent diabetes mellitus.

“…We found that only 32% of the IDDM patients possessed the four susceptibility molecules, all being DR3/4 heterozygotes or DR3/3 or DR4/4 homozygotes. The DQA contribution is probably different in non-Caucasoid populations, as suggested in Japanese (47) or in Black (48) subjects in whom a particular DQa,,3 heterodimer, coded either in cis or in trans position, seems to be involved in disease predisposition.…”

Genetic control of autoimmunity in Type I diabetes and associated disorders

“…Inter-ethnic group studies support the hypothesis of conformational structure influencing diabetogenicity of some HLA alleles or haplotypes. For instance, among the Japanese, the DQB1*0401 allele is usually found on DR4-DQA1*0301-DQB1*0401 haplotypes and is associated with diabetes risk [58]. The DQB1*0401 and DQB1*0402 alleles differ only by one amino acid.…”