STRONG ASSOCIATION BETWEEN DQA1 DQB1 GENOTYPE AND EARLY-ONSET IDDM INCHINESE - THE ASSOCIATION IS WITH ALLELES RATHER THAN SPECIFIC RESIDUES/

We report on the role of HLA-DQA1 and DQB1 alleles in determining susc eptibility to insulin-dependent diabetes mellitus (IDDM) in Hong Kong Chinese and investigate whether these alleles affect the age of onset of the disease. We studied 76 unrelated Chinese patients and 250 contr ols. There was no apparent predisposing effect of non-aspartic acid re sidues at position 57 of the DQ beta chain (Asp(57-)) but there was an excess of homozygous genotypes containing arginine at position 52 of the DQ alpha chain (Arg(52+)). This excess was mainly attributable to the genotype DQA10301/DQA1*05011 in early-onset disease. There was a significant excess of heterodimers of DQ alpha and DQ beta carrying Ar g(52+) and Asp(57-) in both early-onset and late-onset disease, but th e excess in early-onset disease was mainly attributable to a single he terodimer formed by DQA105011 and DQ beta 1*0201. Of three DQA1/DQB1 genotypes containing a double dose of Arg(52+) and Asp(57-), only one had a strong association with both early-onset and late-onset disease. We show that early-onset IDDM and late-onset IDDM in Chinese may be s eparated on the basis of their associated DQA1 and DQB1 genotypes and we conclude that previously reported associations of IDDM with Arg(52) and Asp(57-) residues in Chinese are secondary to specific combinati ons of DQA1 and DQB1 alleles. We also show that DRB1 molecules play a distinct role in determining susceptibility to early-onset IDDM but th e greatest effect is exerted by specific DR/DQ genotypic combinations.