Insulin-dependent diabetes mellitus: HLA-DR and -DQ genotyping in three ethnic groups

Human genomic DNA samples from Caucasoids, Chinese, and Koreans of known serological DR antigen specificity were studied for IDDM-associated variation in HLA-DR and -DQ RFLPs (restriction fragment length polymorphisms). Genotyping allowed for accurate assignment of HLA-DR types and in Caucasoids DRw6 as well as DR2 was unequivocally decreased in IDDM. Further, the universality of certain DR2-associated DQβ subtypes in protection against IDDM was established. HLA-DR3 was found to be increased in IDDM irrespective of whether carried on the B8.DR3 or B18.DR3 haplotype in Caucasoids or on the Bw58.DR3 haplotype in Chinese. These haplotypes have different DRα and DXα arrangements, so the region of susceptibility is confined to DQα, DQβ, DRβ. For HLA-DR4, a 12 kb/DQβ/Bam HI fragment was increased in Caucasoid IDDM, but since this fragment is haplotype specific in Caucasoids and occurs in most healthy DR4- and w9-positive Asians, the 12 kb fragment may be a marker for a DRβ subtype of DR4 associated with IDDM in Caucasoids only. This study has shown the value of ethnic comparisons of HLA-associated diseases, where different linkage disequilibrium relationships have permitted identification of common susceptibility determinants and have provided evidence for some heterogeneity between Caucasoid and Asian populations, in the genetics of IDDM.