Open AccessThe effect of HLA‐DR genes on susceptibility to and severity of ankylosing spondylitis
Author(s) -
Brown Matthew A.,
Kennedy L. Gail,
Darke Chris,
Gibson Kathryn,
Pile Kevin D.,
Shatford Jane L.,
Taylor Andrew,
Calin Andrei,
Wordsworth B. Paul
Publication year - 1998
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(199803)41:3<460::aid-art12>3.0.co;2-x
Subject(s) - ankylosing spondylitis , medicine , odds ratio , spondylitis , relative risk , confidence interval , gastroenterology , human leukocyte antigen , heterozygote advantage , immunology , allele , genetics , biology , gene , antigen
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.