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

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
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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Metadaten
Author:Lina M. Olsson, Anna-Karin Lindqvist, Henrik Källberg, Leonid Padyukov, Harald Burkhardt, Lars Alfredsson, Lars Klareskog, Rikard Holmdahl
URN:urn:nbn:de:hebis:30-57810
DOI:http://dx.doi.org/10.1186/ar2299
ISSN:1465-9913
ISSN:1478-6362
ISSN:1478-6354
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=17897462
Parent Title (English):Arthritis Research & Therapy
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Language:English
Year of Completion:2007
Date of first Publication:2007/09/26
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2008/09/25
Volume:9
Issue:5, Art. R98
Pagenumber:11
First Page:1
Last Page:11
Note:
© 2007 Olsson et al.; licensee BioMed Central Ltd. 
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Source:Arthritis Research & Therapy 2007, 9:R98 ; doi:10.1186/ar2299
HeBIS PPN:205900526
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 2.0

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