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Type: Journal article
Title: The effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis
Author: Brown, M.
Kennedy, L.
Darke, C.
Gibson, K.
Pile, K.
Shatford, J.
Taylor, A.
Calin, A.
Wordsworth, B.
Citation: Arthritis and Rheumatism, 1998; 41(3):460-465
Issue Date: 1998
ISSN: 0004-3591
Statement of
Matthew A. Brown, L. Gail Kennedy, Chris Darke, Kathryn Gibson, Kevin D. Pile, Jane L. Shatford, Andrew Taylor, Andrei Calin, B. Paul Wordsworth
Abstract: Objective: To analyze the effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis (AS). Methods: Three hundred sixty-three white British AS patients were studied; 149 were carefully assessed for a range of clinical manifestations, and disease severity was assessed using a structured questionnaire. Limited HLA class I typing and complete HLA-DR typing were performed using DNA-based methods. HLA data from 13,634 healthy white British bone marrow donors were used for comparison. Results: A significant association between DR1 and AS was found, independent of HLA-B27 (overall odds ratio [OR] 1.4, 95% confidence interval [95% CI] 1.1-1.8, P = 0.02; relative risk [RR] 2.7, 95% CI 1.5-4.8, P = 6 × 10-4 among homozygotes; RR 2.1, 95% CI 1.5-2.8, P = 5 × 10-6 among heterozygotes). A large but weakly significant association between DR8 and AS was noted, particularly among DR8 homozygotes (RR 6.8, 95% CI 1.6-29.2, P = 0.01 among homozygotes; RR 1.6, 95% CI 1.0-2.7, P = 0.07 among heterozygotes). A negative association with DR12 (OR 0.22, 95% CI 0.09-0.5, P = 0.001) was noted. HLA-DR7 was associated with younger age at onset of disease (mean age at onset 18 years for DR7-positive patients and 23 years for DR7-negative patients; Z score 3.21, P = 0.001). No other HLA class I or class II associations with disease severity or with different clinical manifestations of AS were found. Conclusion: The results of this study suggest that HLA-DR genes may have a weak effect on susceptibility to AS independent of HLA-B27, but do not support suggestions that they affect disease severity or different clinical manifestations.
Description: Article first published online: 28 MAY 2004
Rights: © 1998, American College of Rheumatology
RMID: 0030005105
DOI: 10.1002/1529-0131(199803)41:3<460::AID-ART12>3.0.CO;2-X
Published version:;2-X/abstract
Appears in Collections:Medicine publications

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