HLA-DQ primarily confers protection and HLA-DR susceptibility in type I (Insulin-dependent) diabetes studied in population-based affected families and controls
- Univ. of Washington, Seattle (United States) Univ. of Lund (Sweden) Karolinska Institute, Karolinska Hospital, Stockholm (Sweden)
- Universitaet Erlangen-Nuernberg (Germany)
- Univ. of Umeaa (Sweden)
- Hagedorn Research Lab., Gentofte (Denmark)
- Univ. of Washington, Seattle (United States) Karolinska Institute, Karolinska Hospital, Stockholm (Sweden)
The association between HLA-DR and -DQ and insulin-dependent diabetes mellitus (IDDM) in a defined high-incidence area was analyzed in a total of 58 population-based patients, representing 77% of IDDM patients with age at onset below 16 years, and in 92 unrelated parents in control families without IDDM. HLA haplotypes were confirmed by analyzing first-degree relatives in both groups. Seven different methods were used to analyze risk: (1) odds ratio, (2) absolute risk, (3) haplotype relative risk, (4) transcomplementation relative risk, (5) relative predisposing effects, (6) stratification analysis, and (7) test of predisposing allele on haplotype. DQB1*0302 indicated somewhat higher risk than did DR4, while DR3 had a higher risk than DQB1*0201; however, the 95% confidence intervals of the risk estimates overlapped. The positive association between IDDM and the DQB1*0201-DQA1*0501-DR3 haplotype seems to be due to DR3 or to an unknown linked gene. More important, DQA1*0301 was present among 93% of the patients, and this allele in various transcomplementation combinations with DQBL alleles showed closer association to IDDM than did any other alleles. The strong negative association of the DQB1*0602 allele also in the presence of either DR4 or DQBI*0302 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 susceptibility, perhaps by induction of autoreactive T lymphocytes. 67 refs., 3 figs., 9 tabs.
- OSTI ID:
- 5941369
- Journal Information:
- American Journal of Human Genetics; (United States), Vol. 53:1; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
Similar Records
HLA class II DR-DQ amino acids and insulin-dependent diabetes mellitus: Application of the haplotype method
No difference in the parental origin of susceptibility HLA class II haplotypes among Norwegian patients with insulin-dependent diabetes mellitus