Complex interaction between HLA DR and DQ in conferring risk for childhood type 1 diabetes
Kockum, I. ; Sanjeevi, C. B. ; Eastman, S. ; Landin-Olsson, M. LU ; Dahlquist, G. and Lernmark, Åke LU
(1999)
In European Journal of Immunogenetics
26(5).
p.361-372
- Abstract
Type 1 (insulin-dependent) diabetes mellitus is associated with HLA DR and DQ factors, but the primary risk alleles are difficult to identify because recombination events are rare in the DQ-DR region. The risk of HLA genotypes for type 1 diabetes was therefore studied in more than 420 incident new onset, population-based type 1 diabetes children and 340 age, sex and geographically matched controls from Sweden. A stepwise approach was used to analyse risk by relative and absolute risks, stratification analysis and the predispositional allele test. The strongest relative and absolute risks were observed for DQB1*02-DQA1*0501/DQB1*0302-DQA1*0301 heterozygotes (AR 1/46, P < 0.001) or the simultaneous presence of both DRB1*03 and... (More)
Type 1 (insulin-dependent) diabetes mellitus is associated with HLA DR and DQ factors, but the primary risk alleles are difficult to identify because recombination events are rare in the DQ-DR region. The risk of HLA genotypes for type 1 diabetes was therefore studied in more than 420 incident new onset, population-based type 1 diabetes children and 340 age, sex and geographically matched controls from Sweden. A stepwise approach was used to analyse risk by relative and absolute risks, stratification analysis and the predispositional allele test. The strongest relative and absolute risks were observed for DQB1*02-DQA1*0501/DQB1*0302-DQA1*0301 heterozygotes (AR 1/46, P < 0.001) or the simultaneous presence of both DRB1*03 and DQB1*0302 (AR 1/52, P < 0.001). Stratification analysis showed that DQB1*0302 was more frequent among DRB1*04 patients than DRB1*04 controls (P < 0.001), while DRB1*03 was more frequent among both DQA1*0501 (P < 0.001) and DQB1*02 (P < 0.001) patients than respective controls. The predispositional allele test indicated that DRB1*03 (P < 0.001) would be the predominant risk factor on the DRB1*03-DQA1*0501-DQB1*02 haplotype. In contrast, although DQB1*0302 (P < 0.001) would be the predominant risk factor on the DRB1*04-DQA1*0301-DQB1*0302 haplotype, the predispositional allele test also showed that DRB1*0401, but no other DRB1*04 subtype, had an additive risk to that of DQB1*0302 (P < 0.002). It is concluded that the association between type 1 diabetes and HLA is due to a complex interaction between DR and DQ since (1) DRB1*03 was more strongly associated with the disease than DQA1*0501-DQB1*02 and (2) DRB1*0401 had an additive effect to DQB1*0302. The data from this population-based investigation suggest an independent role of DR in the risk of developing type 1 diabetes, perhaps by providing diseases-promoting transcomplementation molecules.
(Less)
- author
- Kockum, I.
; Sanjeevi, C. B.
; Eastman, S.
; Landin-Olsson, M.
LU
; Dahlquist, G.
and Lernmark, Åke
LU
- organization
- publishing date
- 1999-10-23
- type
- Contribution to journal
- publication status
- published
- subject
- in
- European Journal of Immunogenetics
- volume
- 26
- issue
- 5
- pages
- 12 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:10553503
- scopus:0032851029
- ISSN
- 0960-7420
- DOI
- 10.1046/j.1365-2370.1999.00173.x
- language
- English
- LU publication?
- yes
- id
- 2fc82337-66a1-4a6d-9652-34691003ea2a
- date added to LUP
- 2019-06-30 23:34:49
- date last changed
- 2025-01-23 22:07:55
@article{2fc82337-66a1-4a6d-9652-34691003ea2a,
abstract = {{<p>Type 1 (insulin-dependent) diabetes mellitus is associated with HLA DR and DQ factors, but the primary risk alleles are difficult to identify because recombination events are rare in the DQ-DR region. The risk of HLA genotypes for type 1 diabetes was therefore studied in more than 420 incident new onset, population-based type 1 diabetes children and 340 age, sex and geographically matched controls from Sweden. A stepwise approach was used to analyse risk by relative and absolute risks, stratification analysis and the predispositional allele test. The strongest relative and absolute risks were observed for DQB1*02-DQA1*0501/DQB1*0302-DQA1*0301 heterozygotes (AR 1/46, P < 0.001) or the simultaneous presence of both DRB1*03 and DQB1*0302 (AR 1/52, P < 0.001). Stratification analysis showed that DQB1*0302 was more frequent among DRB1*04 patients than DRB1*04 controls (P < 0.001), while DRB1*03 was more frequent among both DQA1*0501 (P < 0.001) and DQB1*02 (P < 0.001) patients than respective controls. The predispositional allele test indicated that DRB1*03 (P < 0.001) would be the predominant risk factor on the DRB1*03-DQA1*0501-DQB1*02 haplotype. In contrast, although DQB1*0302 (P < 0.001) would be the predominant risk factor on the DRB1*04-DQA1*0301-DQB1*0302 haplotype, the predispositional allele test also showed that DRB1*0401, but no other DRB1*04 subtype, had an additive risk to that of DQB1*0302 (P < 0.002). It is concluded that the association between type 1 diabetes and HLA is due to a complex interaction between DR and DQ since (1) DRB1*03 was more strongly associated with the disease than DQA1*0501-DQB1*02 and (2) DRB1*0401 had an additive effect to DQB1*0302. The data from this population-based investigation suggest an independent role of DR in the risk of developing type 1 diabetes, perhaps by providing diseases-promoting transcomplementation molecules.</p>}},
author = {{Kockum, I. and Sanjeevi, C. B. and Eastman, S. and Landin-Olsson, M. and Dahlquist, G. and Lernmark, Åke}},
issn = {{0960-7420}},
language = {{eng}},
month = {{10}},
number = {{5}},
pages = {{361--372}},
publisher = {{Wiley-Blackwell}},
series = {{European Journal of Immunogenetics}},
title = {{Complex interaction between HLA DR and DQ in conferring risk for childhood type 1 diabetes}},
url = {{http://dx.doi.org/10.1046/j.1365-2370.1999.00173.x}},
doi = {{10.1046/j.1365-2370.1999.00173.x}},
volume = {{26}},
year = {{1999}},
}