HLA-DQ antigens and DQ beta amino acid 57 of Japanese patients with insulin-dependent diabetes mellitus: detection of a DRw8DQw8 haplotype.

DQw8 (DQw3.2) on DR4 haplotypes is a susceptibility gene for development of insulin-dependent diabetes mellitus (IDDM) in Caucasoids, possibly because it encodes a non-Asp amino acid (aa) (i.e. Ala) at residue 57 of the DQ beta chain (non-Asp-57). Most Caucasoid IDDM patients are homozygous non-Asp-57. We have examined 14 Japanese IDDM patients, selected to be either DR4 or DRw9 (associated to IDDM among Japanese). Their DQB1 alleles and the aa encoded by their DQB1 codons 57 were identified, using 11 different sequence-specific oligonucleotide probes. Secondly, they were examined with DQw8 specific T lymphocyte clones and with anti-DQ monoclonal antibodies. The DQB1 genes on their DR4 and DRw9 haplotypes in all cases encoded Asp-57. Two patients were Asp-57 homozygous, the rest were Asp-57/non-Asp-57 heterozygous. The DR4 haplotypes all carried DQw4 (rather than DQw8), and the DRw9 haplotypes all carried DQw9. Furthermore, five of six DRw8 positive patients carried a previously undetected DRw8DQw8 haplotype, where both the DQA1 and DQB1 genes were similar to those usually found on the DR4DQw8 haplotype. Thus, the DR/DQ allele combinations and aa residue 57 of the DQ beta chain of Caucasoid and Japanese IDDM patients are largely different.