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A meta-analysis of interleukin-6 promoter polymorphisms on risk of hip and knee osteoarthritis

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Valdes, Ana M., Arden, N. (Nigel), Tamm, A., Kisand, Kalle, Doherty, Sally A., Pola, E., Cooper, C., Tamm, A., Muir, Kenneth (Kenneth R.), Kerna, Irina, Hart, D., O'Neil, F., Zhang, W., Spector, T. D. (Timothy David), Maciewicz, Rose A. and Doherty, M., M.D.. (2010) A meta-analysis of interleukin-6 promoter polymorphisms on risk of hip and knee osteoarthritis. Osteoarthritis and Cartilage, Vol.18 (No.5). pp. 699-704. ISSN 1063-4584

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Official URL: http://dx.doi.org/10.1016/j.joca.2009.12.012

Abstract

Objective: Interleukin-6 is a pro-inflammatory cytokine involved in the pathogenesis of osteoarthritis (OA). We investigated the role of two single nucleotide polymorphisms (SNPs) mapping to the promoter of the IL-6 gene on genetic susceptibility to hip and knee OA. Methods: The -174 G/C (rs1800795) and -597 G/A (rs1800797) SNPs, implicated in the literature in risk of hip and hand OA, were genotyped in 2511 controls, 1101 hip OA cases and 1904 knee OA cases from four cohorts from the UK and Estonia. Data were analysed in conjuntion with published data on rs1800797 from the Genetics of OA and Lifestyle study (UK) on 791 controls. 1034 knee and 997 hip OA cases and rs1800795 data on 75 hip OA cases and 96 controls from Italy. Cases included both radiographic OA only and radiographic and symptomatic OA. Fixed and random-effects meta-analysis models were tested. Results: No significant association was found with hip OA or knee OA with either SNP nor with the haplotypes formed by them. For individual SNPs the smallest P-value for hip OA was observed using a random-effects model for rs1800795 ORG allele = 1.066 (95% CI 0.89-1.28) P < 0.49, and significant heterogeneity between cohorts (I-2 = 65%, P < 0.034) was detected. For knee OA the smallest P-value was seen for rs1800797 ORA allele = 1.055 (95%CI 0.98-1.12) P < 0.18, no significant heterogeneity was observed (I-2 = 0%, P < 0.68). Conclusions: Our data do not support a role for the -174 and -597 IL-6 promoter polymorphisms in genetic susceptibility to knee or hip OA in Caucasian populations. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Item Type: Journal Article
Subjects: R Medicine > RC Internal medicine
Divisions: Faculty of Medicine > Warwick Medical School
Journal or Publication Title: Osteoarthritis and Cartilage
Publisher: Elsevier Science BV
ISSN: 1063-4584
Date: May 2010
Volume: Vol.18
Number: No.5
Number of Pages: 6
Page Range: pp. 699-704
Identification Number: 10.1016/j.joca.2009.12.012
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: EC, Arthritis Research Campaign (UK), Medical Research Council (UK), Oxford NIHR Musculoskeletal Biomedical Research Unit, Estonian Science Foundation, Estonian Ministry of Social Affairs, AstraZeneca Macclesfield UK
Grant number: 200800, 5308, 9.6-4/2035, 12.1-5/597
URI: http://wrap.warwick.ac.uk/id/eprint/5763

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