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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 5/2007

Open Access 01-10-2007 | Research article

A case-control study of rheumatoid arthritis identifies an associated single nucleotide polymorphism in the NCF4 gene, supporting a role for the NADPH-oxidase complex in autoimmunity

Authors: Lina M Olsson, Anna-Karin Lindqvist, Henrik Källberg, Leonid Padyukov, Harald Burkhardt, Lars Alfredsson, Lars Klareskog, Rikard Holmdahl

Published in: Arthritis Research & Therapy | Issue 5/2007

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Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease with a heritability of 60%. Genetic contributions to RA are made by multiple genes, but only a few gene associations have yet been confirmed. By studying animal models, reduced capacity of the NADPH-oxidase (NOX) complex, caused by a single nucleotide polymorphism (SNP) in one of its components (the NCF1 gene), has been found to increase severity of arthritis. To our knowledge, however, no studies investigating the potential role played by reduced reactive oxygen species production in human RA have yet been reported. In order to examine the role played by the NOX complex in RA, we investigated the association of 51 SNPs in five genes of the NOX complex (CYBB, CYBA, NCF4, NCF2, and RAC2) in a Swedish case-control cohort consisting of 1,842 RA cases and 1,038 control individuals. Several SNPs were found to be mildly associated in men in NCF4 (rs729749, P = 0.001), NCF2 (rs789181, P = 0.02) and RAC2 (rs1476002, P = 0.05). No associations were detected in CYBA or CYBB. By stratifying for autoantibody status, we identified a strong association for rs729749 (in NCF4) in autoantibody negative disease, with the strongest association detected in rheumatoid factor negative men (CT genotype versus CC genotype: odds ratio 0.34, 95% confidence interval 0.2 to 0.6; P = 0.0001). To our knowledge, this is the first genetic association identified between RA and the NOX complex, and it supports previous findings from animal models of the importance of reactive oxygen species production capacity to the development of arthritis.
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Metadata
Title
A case-control study of rheumatoid arthritis identifies an associated single nucleotide polymorphism in the NCF4 gene, supporting a role for the NADPH-oxidase complex in autoimmunity
Authors
Lina M Olsson
Anna-Karin Lindqvist
Henrik Källberg
Leonid Padyukov
Harald Burkhardt
Lars Alfredsson
Lars Klareskog
Rikard Holmdahl
Publication date
01-10-2007
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 5/2007
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2299

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