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Evidence of epistasis between Interleukin-1 and Selenoprotein-S with susceptibility to rheumatoid arthritis

Marinou, L., Walters, K., Dickson, M.C., Binks, M.H., Montgomery, D.S. and Wilson, A.G. (2009) Evidence of epistasis between Interleukin-1 and Selenoprotein-S with susceptibility to rheumatoid arthritis. Annals of the Rheumatic Diseases , 68. pp. 1494-1497. ISSN 0003-4967

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Objective: Selenoprotein-S (SELS) is involved in the stress response within the endoplasmic reticulum (ER) and inflammation. Recently, promoter variants in the SELS gene were shown to be associated with plasma levels of interleukin (IL)6, IL1β and tumour necrosis factor (TNF). It was hypothesised that these variants could influence rheumatoid arthritis (RA) susceptibility and may interact with functional single nucleotide polymorphisms (SNPs) in the genes for IL1, IL6 and TNF.

Methods: Genotyping was performed in 988 unrelated healthy controls and 965 patients with RA. Stratified analysis was used to test for interactions. Single gene effects and evidence of epistasis were investigated using the Mantel–Haenszel (M–H) test and the linkage disequilibrium (LD)-based statistic.

Results: No association of SELS −105 genotype and RA susceptibility was detected. Stratification of SELS −105 genotypes by IL1 −511 genotypes showed that the disease risk (comparing AA/GA to GG at the SELS −105 locus) in individuals with the GG/AG genotype at the IL1β −511 locus was significantly lower than that in individuals having the AA genotype at the IL1β −511 locus (odds ratio (OR): 0.9 and 2.3, respectively; p = 0.004 by M–H test). Significant epistasis was also detected using the LD-based statistic (p = <0.001). No interaction was observed between SELS −105 and IL6 or TNF variants.

Conclusion: Our results reveal evidence of strong epistasis in two genes in the IL1 production pathway and highlight the potential importance of gene–gene interactions in the pathogenesis of RA.

Item Type: Article
Copyright, Publisher and Additional Information: © 2009 BMJ. Reproduced in accordance with the publisher's self-archiving policy.
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Science (Sheffield) > School of Mathematics and Statistics (Sheffield)
Depositing User: Mrs Megan Hobbs
Date Deposited: 19 Mar 2010 10:43
Last Modified: 01 Dec 2015 04:10
Published Version: http://dx.doi.org/10.1136/ard.2008.090001
Status: Published
Publisher: BMJ Publishing Group
Refereed: Yes
Identification Number: 10.1136/ard.2008.090001
URI: http://eprints.whiterose.ac.uk/id/eprint/10634

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