PT  - JOURNAL ARTICLE
AU  - A-M Sims
AU  - A E Timms
AU  - J Bruges-Armas
AU  - R Burgos-Vargas
AU  - C-T Chou
AU  - T Doan
AU  - A Dowling
AU  - R N Fialho
AU  - P Gergely
AU  - D D Gladman
AU  - R Inman
AU  - M Kauppi
AU  - K Kaarela
AU  - K Laiho
AU  - W Maksymowych
AU  - J J Pointon
AU  - P Rahman
AU  - J D Reveille
AU  - R Sorrentino
AU  - J Tuomilehto
AU  - G Vargas-Alarcon
AU  - B P Wordsworth
AU  - H Xu
AU  - M A Brown
AU  - on behalf of the International Genetics of Ankylosing Spondylitis
TI  - Prospective meta-analysis of interleukin 1 gene complex polymorphisms confirms associations with ankylosing spondylitis
AID  - 10.1136/ard.2007.081364
DP  - 2008 Sep 01
TA  - Annals of the Rheumatic Diseases
PG  - 1305--1309
VI  - 67
IP  - 9
4099  - http://ard.bmj.com/content/67/9/1305.short
4100  - http://ard.bmj.com/content/67/9/1305.full
SO  - Ann Rheum Dis2008 Sep 01; 67
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.