The effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis

Arthritis Rheum. 1998 Mar;41(3):460-5. doi: 10.1002/1529-0131(199803)41:3<460::AID-ART12>3.0.CO;2-X.


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 x 10(-4) among homozygotes; RR 2.1, 95% CI 1.5-2.8, P = 5 x 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Arthritis / genetics
  • Genetic Predisposition to Disease
  • HLA-DR Antigens / genetics*
  • Heterozygote
  • Homozygote
  • Humans
  • Risk Factors
  • Spondylitis, Ankylosing / epidemiology
  • Spondylitis, Ankylosing / genetics*
  • Spondylitis, Ankylosing / physiopathology*


  • HLA-DR Antigens