PCR-RFLP ANALYSIS OF HLA GENES IN JAPANESE PATIENTS WITH INSULIN-DEPENDENT DIABETES MELLITUS

The HLA class II (DQA1, DQB1, DRB1 and DPB1) genes of 28 unrelated Japanese insulindependent diabetes mellitus (IDDM) patients and 27 healthy control subjects were typed by PCR-RFLP (polymerase chain reaction-restriction length polymorphism). DQA1*0301, DQB1*0303, DQB1*0401 and DRB1*0405 were positively, and DQA1*0103 and DQB1*0601 were negatively associated with IDDM. There was no specific association between IDDM and the DPB1 allele. Haplotypes determined according to the published linkage disequilibrium in the Japanese population showed that DQA1*0301-DQB1*0303-DRB1*0901 and DQA1*0301-DQB1*0401-DRB1*0405 were increased in IDDM patients. Twenty-four of the IDDM patients had either of the two haplotypes, while only six of the control subjects did. The homozygosity of non-aspartic acid at position 57 of the DR beta chain increased susceptibility to IDDM, while aspartic acid at position 57 of the DQ beta chain did not protect Japanese against IDDM. Homozygosity of arginine at position 52 of the DQ alpha chain was increased in IDDM. These findings suggest that, *DQA1*0301 and arginine at position 52 of the DQ alpha chain increase the susceptibility to IDDM in Japanese as in caucasian and black populations, but that DRB1*0405 and non-aspartic acid at position 57 of the DR beta chain, rather than DQB1 allele and non-aspartic acid at position 57 of the DQ beta chain, also influence the susceptibility of Japanese to IDDM.