title: Association between the interleukin 23 receptor and ankylosing spondylitis is confirmed by a new UK case-control study and meta-analysis of published series.
abstract: OBJECTIVE
  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 approximately 1.2) but also with rs11209026 (P < 10(-10), OR approximately 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.
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University Institute of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford, UK.
authors.forename: Tugce
authors.initials: T
authors.lastname: Karaderi
authors.forename: David
authors.initials: D
authors.lastname: Harvey
authors.forename: Claire
authors.initials: C
authors.lastname: Farrar
authors.forename: Louise H
authors.initials: LH
authors.lastname: Appleton
authors.forename: Millicent A
authors.initials: MA
authors.lastname: Stone
authors.forename: Roger D
authors.initials: RD
authors.lastname: Sturrock
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
authors.forename: Paul
authors.initials: P
authors.lastname: Wordsworth
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Pointon
mesh_terms: D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics*; D013167:Spondylitis, Ankylosing / Q000235:genetics*; D006113:United Kingdom
chemical_list: C515500:IL23R protein, human; D018123:Receptors, Interleukin