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


CONCLUSIONS
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.
Brown
M A
MA
Wellcome Trust Centre for Human Genetics, Headington, UK.
Kennedy
L G
LG
Darke
C
C
Gibson
K
K
Pile
K D
KD
Shatford
J L
JL
Taylor
A
A
Calin
A
A
Wordsworth
B P
BP
D017668:Age of Onset; D001168:Arthritis / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D012307:Risk Factors; D013167:Spondylitis, Ankylosing / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*
D006684:HLA-DR Antigens