Strong Association of HLA-DR3/DRw9 Heterozygosity With Early-Onset Insulin-Dependent Diabetes Mellitus in Chinese

Studies of Caucasian and Japanese patients with insulin-dependent diabetes mellitus (IDDM) have shown that heterozygosity for certain HLA-DR antigens confers a high risk of developing the disease. The HLA antigens of 75 Chinese patients and 100 Chinese controls in Hong Kong were studied to investigate the role of HLA-DR heterozygosity in Chinese individuals. Some of the patients and controls were also tested for allotypic variation in the complement components C2, C4, and BF. Three alleles, Aw33, B17, and DR3, had increased frequencies in patients compared with controls and frequently occurred together in the same phenotype, which suggested their existence as a haplotype. There were no statistically significant differences in complement allotype frequencies between patients and controls, although the C4B null allele seemed to be associated with Aw33, B17, and DR3. No other HLA-DR antigen appeared to be associated with IDDM. However, when the patients were separated on the basis of age at onset, the frequency of DR3/DRw9 heterozygosity was markedly increased in patients presenting in the first decade of life, but there was no increase in patients presenting at >20 yr of age. DRw9 is strongly associated with autoimmune disease in Chinese, whereas DR3 is not. We suggest that the major IDDM susceptibility locus in Chinese is associated with HLA-DR3 and that patients with HLA-DR3 and HLA-DRw9 have an added predisposition to autoimmune disease and therefore develop IDDM earlier than patients without DRw9.