Diversity in HLA-DR4-related DR,DQ haplotypes in Australia, Oceania, and China.

The relative distributions of 12 HLA-DR4-related DRB1 alleles in indigenous populations of Australia, Melanesia, Micronesia, Polynesia, and northern and southern China have been determined by analysis of oligonucleotide hybridization patterns of 406 examples of HLA-DR4. DRB10405 and DRB10410 were common DR4 alleles in Australian aborigines and in Melanesians, while DRB10403 was the predominant DR4 allele in coastal Melanesians, Micronesians, and Polynesians; DRB10406 was confined to Chinese. A novel DR4 allele, found in 30% of DR4-positive Australian aborigines but exclusive to one aboriginal population, was a combination of DRB1*04 and 0803 nucleotide sequences and was carried on a haplotype with DR4-like DQ linkage arrangements. DQA1 and DQB1 typing generated 12 DR4-related haplotypes; the population distributions of these reflected the ancestral affinities of aborigines and Melanesians, the overlaying of coastal Melanesia with pre-Polynesian DR4 alleles and the colonization of Micronesia by an independent, non-Polynesian group. DR4-related autoimmune disorders such as rheumatoid arthritis (RA) and insulin-dependent diabetes mellitus (IDDM) are virtually unknown in indigenous populations of Australia and Oceania and this study confirmed that high-risk RA determinants, Dw4 and Dw14, occurred rarely. However, the DQw8 allele, thought particularly to predispose to IDDM, was present in the majority of DR4-positive Polynesians and Micronesians.