RT Journal Article SR Electronic T1 Prospective meta-analysis of interleukin 1 gene complex polymorphisms confirms associations with ankylosing spondylitis JF Annals of the Rheumatic Diseases JO Ann Rheum Dis FD BMJ Publishing Group Ltd and European League Against Rheumatism SP 1305 OP 1309 DO 10.1136/ard.2007.081364 VO 67 IS 9 A1 A-M Sims A1 A E Timms A1 J Bruges-Armas A1 R Burgos-Vargas A1 C-T Chou A1 T Doan A1 A Dowling A1 R N Fialho A1 P Gergely A1 D D Gladman A1 R Inman A1 M Kauppi A1 K Kaarela A1 K Laiho A1 W Maksymowych A1 J J Pointon A1 P Rahman A1 J D Reveille A1 R Sorrentino A1 J Tuomilehto A1 G Vargas-Alarcon A1 B P Wordsworth A1 H Xu A1 M A Brown A1 on behalf of the International Genetics of Ankylosing Spondylitis YR 2008 UL http://ard.bmj.com/content/67/9/1305.abstract AB Objectives: The aim of the current study was to determine the contribution of interleukin (IL)1 gene cluster polymorphisms previously implicated in susceptibility for ankylosing spondylitis (AS) to AS susceptibility in different populations worldwide.Methods: Nine polymorphisms in the IL1 gene cluster members IL1A (rs2856836, rs17561 and rs1894399), IL1B (rs16944), IL1F10 (rs3811058) and IL1RN (rs419598, the IL1RA VNTR, rs315952 and rs315951) were genotyped in 2675 AS cases and 2592 healthy controls recruited in 12 different centres in 10 countries. Association of variants with AS was tested by Mantel–Haenszel random effects analysis.Results: Strong association was observed with three single nucleotide polymorphisms (SNPs) in the IL1A gene (rs2856836, rs17561, rs1894399, p = 0.0036, 0.000019 and 0.0003, respectively). There was no evidence of significant heterogeneity of effects between centres, and no evidence of non-combinability of findings. The population attributable risk fraction of these variants in Caucasians is estimated at 4–6%.Conclusions: This study confirms that IL1A is associated with susceptibility to AS. Association of the other IL1 gene complex members could not be excluded in specific populations. Prospective meta-analysis is a useful tool in confirmation studies of genes associated with complex genetic disorders such as AS, providing sufficiently large sample sizes to produce robust findings often not achieved in smaller individual cohorts.