Rheumatology Advance Access originally published online on February 2, 2009
Rheumatology 2009 48(4):386-389; doi:10.1093/rheumatology/ken501
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Association between the interleukin 23 receptor and ankylosing spondylitis is confirmed by a new UK case–control study and meta-analysis of published series
1Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University Institute of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford, 2Royal National Hospital for Rheumatic Diseases, Bath, 3Department of Immunology, Infection and Inflammation, Centre for Rheumatic Diseases, University of Glasgow, Glasgow, UK and 4Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Queensland, Australia.
Correspondence to: Jennifer J. Pointon, Oxford University Institute of Musculoskeletal Science, Botnar Research Centre, Nuffield Orthopaedic Centre, Windmill Road, Headington, Oxford OX3 7LD, UK. E-mail: jennyp{at}well.ox.ac.uk
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Abstract |
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Objectives. It has been shown previously that IL-23R variants are associated with AS. We conducted an extended analysis in the UK population and a meta-analysis with the previously published studies, in order to refine these IL-23R associations with AS.
Methods. The UK case–control study included 730 new cases and 1331 healthy controls. In the extended study, the 730 cases were combined with 1088 published cases. Allelic associations were analysed using contingency tables. In the meta-analysis, 3482 cases and 3150 controls from four different published studies and the new UK cases were combined. DerSimonian–Laird test was used to calculate random effects pooled odds ratios (ORs).
Results. In the UK case–control study with new cases, four of the eight SNPs showed significant associations, whereas in the extended UK study, seven of the eight IL-23R SNPs showed significant associations (P < 0.05) with AS, maximal with rs11209032 (P < 10–5, OR 1.3), when cases with IBD and/or psoriasis were excluded. The meta-analysis showed significant associations with all eight SNPs; the strongest associations were again seen not only with rs11209032 (P = 4.06 x 10–9, OR 
1.2) but also with rs11209026 (P < 10–10, OR 0.6).
Conclusions. IL-23R polymorphisms are clearly associated with AS, but the primary causal association(s) is(are) still not established. These polymorphisms could contribute either increased or decreased susceptibility to AS; functional studies will be required for their full evaluation. Additionally, observed stronger associations with SNPs rs11209026 and rs11465804 upon exclusion of IBD and/or psoriasis cases may represent an independent association with AS.
KEY WORDS: IL-23 receptor, AS, Polymorphism, SpA, Genetic association
Submitted 29 August 2008;
revised version accepted 10 December 2008.
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