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 greater than 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.