HLA-DQ PRIMARILY CONFERS PROTECTION AND HLA-DR SUSCEPTIBILITY IN TYPE-I (INSULIN-DEPENDENT) DIABETES STUDIED IN POPULATION-BASED AFFECTED FAMILIES AND CONTROLS

The association between HLA-DR and -DQ and insulin-dependent diabetes mellitus (IDDM) in a defined high-incidence area was analyzed in a tot al of 58 population-based patients, representing 77% of IDDM patients with age at onset below 16 years, and in 92 unrelated parents in contr ol families without IDDM. HLA haplotypes were confirmed by analyzing f irst-degree relatives in both groups. Seven different methods were use d to analyze risk: (1) odds ratio, (2) absolute risk, (3) haplotype re lative risk, (4) transcomplementation relative risk, (5) relative pred isposing effects, (6) stratification analysis, and (7) test of predisp osing allele on haplotype. DQB10302 indicated somewhat higher risk th an did DR4, while DR3 had a higher risk than DQB10201; however, the 9 5% confidence intervals of the risk estimates overlapped. The positive association between IDDM and the DQB10201-DQA1*0501-DR3 haplotype se ems to be due to DR3 or to an unknown linked gene. More important, DQA 10301 was present among 93% of the patients, and this allele in vario us transcomplementation combinations with DQB1 alleles showed closer a ssociation to IDDM than did any other alleles. The strong negative ass ociation of the DQB10602 allele also in the presence of either DR4 or DQB10302 or both suggests that, in a high-risk population for IDDM, HLA-DQ primarily confers protection, perhaps by induction of tolerance . Consistent with known functions, HLA-DR may primarily confer suscept ibility, perhaps by induction of autoreactive T lymphocytes.