HLA-DQ primarily confers protection and HLA-DR susceptibility in type I (insulin-dependent) diabetes studied in population-based affected families and controls
(1993) In American Journal of Human Genetics 53(1). p.150-167- Abstract
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... (More)
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 DQB1 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 DQB1*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.
(Less)
- author
- Kockum, I. ; Wassmuth, R. ; Holmberg, E. ; Michelsen, B. and Lernmark, A. LU
- publishing date
- 1993-01-01
- type
- Contribution to journal
- publication status
- published
- in
- American Journal of Human Genetics
- volume
- 53
- issue
- 1
- pages
- 150 - 167
- publisher
- Cell Press
- external identifiers
-
- pmid:8317480
- scopus:0027420431
- ISSN
- 0002-9297
- language
- English
- LU publication?
- no
- id
- 4b757cc2-51aa-47f5-8ec8-0b9a8f30a2ee
- date added to LUP
- 2019-09-11 09:26:49
- date last changed
- 2024-03-13 08:09:55
@article{4b757cc2-51aa-47f5-8ec8-0b9a8f30a2ee, abstract = {{<p>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 DQB1 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 DQB1*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.</p>}}, author = {{Kockum, I. and Wassmuth, R. and Holmberg, E. and Michelsen, B. and Lernmark, A.}}, issn = {{0002-9297}}, language = {{eng}}, month = {{01}}, number = {{1}}, pages = {{150--167}}, publisher = {{Cell Press}}, series = {{American Journal of Human Genetics}}, title = {{HLA-DQ primarily confers protection and HLA-DR susceptibility in type I (insulin-dependent) diabetes studied in population-based affected families and controls}}, volume = {{53}}, year = {{1993}}, }