GENES FOR INSULIN-DEPENDENT DIABETES-MELLITUS (IDDM) IN THE MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) OF AFRICAN-AMERICANS

Mapping the MHC-associated susceptibility and resistance factors for insulin-dependent diabetes mellitus (IDDM) has been difficult due to the strong linkage disequilibrium within the HLA-DR-DQ region. Previous analyses have suggested that the study of IDDM-associated haplotypes in different races might be useful for identifying the responsible genes. We have performed complete HLA class II genotyping to study susceptibility and resistance to IDDM in 34 randomly selected African-American IDDM patients and 69 ethnically-matched controls. IDDM patients showed highly significant increases of DRB1*0301, DRB1*0401, DRB1*0405, DQA1*0301, DQA1*0302, DQB1*0201 and DQB1*0302. Analysis of DQA1-DQB1 associations showed that DQA1*03 combined with both DQB1*0201 and DQB1*0302 gave the highest odds ratio, suggesting a synergistic effect due to formation of heterodimers encoded both in cis and in trans. Among the subsets of DR4, only DRB1*0401 and DRB1*0405 were increased in diabetic patients. Interestingly, DQB1*0602 and DQB1*0301, which have previously been thought to encode resistance factors in Caucasians, were not significantly decreased and, after removal of known susceptibility haplotypes, were found to have essentially identical frequencies in patients and controls.