Prospective meta-analysis of interleukin 1 gene complex polymorphisms confirms associations with ankylosing spondylitis

Sims, A. M., Timms, A. E., Bruges-Armas, J., Burgos-Vargas, R., Chou, C. T., Doan, T., Dowling, A., Fialho, R. N., Gergely, P., Gladman, D. D., Inman, R., Kauppi, M., Kaarela, K., Laiho, K., Maksymowych, W., Pointon, J. J., Rahman, P., Reveille, J. D., Sorrentino, R., Tuomilehto, J., Vargas-Alarcon, G., Wordsworth, B. P., Xu, H., & Brown, M A (2008) Prospective meta-analysis of interleukin 1 gene complex polymorphisms confirms associations with ankylosing spondylitis. Annals of the Rheumatic Diseases, 67(9), pp. 1305-1309.

View at publisher


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.

Impact and interest:

75 citations in Scopus
Search Google Scholar™
62 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 87748
Item Type: Journal Article
Refereed: Yes
Additional Information: No file attached.
Additional URLs:
Keywords: interleukin 1, allele, ankylosing spondylitis, article, controlled study, disease predisposition, DNA polymorphism, gene cluster, gene frequency, gene linkage disequilibrium, genetic variability, human, priority journal, single nucleotide polymorphism, Genetic Predisposition to Disease, Genotype, Humans, Interleukin-1, Interleukin-1alpha, Multigene Family, Polymorphism, Single Nucleotide, Prospective Studies, Spondylitis, Ankylosing
DOI: 10.1136/ard.2007.081364
ISSN: 0003-4967
Deposited On: 24 Sep 2015 04:12
Last Modified: 25 Sep 2015 03:15

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page