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Rheumatology 2001; 40: 1359-1364
© 2001 British Society for Rheumatology
Original Papers |
A polymorphism within the interleukin 1 receptor antagonist (IL-1Ra) gene is associated with ankylosing spondylitis
Centre for Rheumatic Diseases, University Department of Medicine, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER and
1 Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Glasgow G11 6NT, UK
Objective. Genetic factors that predispose individuals to ankylosing spondylitis (AS) are not fully understood, but are unlikely to be restricted to HLA-B27. Proinflammatory cytokines are implicated in the development of sacroiliitis. We have examined the allele frequencies of three polymorphic sites in the interleukin (IL)-1 genes in AS patients to investigate whether genetic regulation of IL-1 production could be implicated in AS pathogenesis.
Methods. DNA from 188 AS patients, 115 healthy controls and 81 HLA-B27-positive healthy controls, all from the West of Scotland, were examined with the polymerase chain reaction in a case-controlled study. Polymorphic sites in genes of the IL-1 family were examined, including the 86-base pair variable number tandem repeat within intron 2 of the IL-1Ra gene, and the restriction fragment length polymorphisms at positions -889 in the IL-1
gene and -511 in the IL-1ß gene.
Results. No significant differences were seen at the polymorphic alleles in the IL-1 and IL-1ß genes, but there was a significant increase in the carriage of allele 2 in the IL-1Ra in the AS patients compared with local controls (16 vs 8%, odds ratio 2.3, 95% confidence interval 1.2–4.4, P=0.01).
Conclusion. This report of an association with a polymorphic site within the IL-1 locus and AS suggests that genes other than B27 may well be involved in the pathogenesis of AS.
KEY WORDS: Ankylosing, spondylitis, Interleukin 1, Genetics, Restriction fragment length polymorphism, Variable number tandem repeat.
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