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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.The -174G/C (rs1800795) and -597G/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.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 OR(Gallele)=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 OR(Aallele)=1.055 (95%CI 0.98-1.12) P<0.18, no significant heterogeneity was observed (I(2)=0%, P<0.68).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.

Original publication

DOI

10.1016/j.joca.2009.12.012

Type

Journal article

Journal

Osteoarthritis and cartilage

Publication Date

05/2010

Volume

18

Pages

699 - 704

Addresses

Department of Twin Research, St. Thomas' Hospital Campus, Kings College London School of Medicine London, UK. ana.valdes@kcl.ac.uk

Keywords

Humans, Osteoarthritis, Knee, Osteoarthritis, Hip, Genetic Predisposition to Disease, Interleukin-6, Risk Factors, Cohort Studies, Gene Frequency, Genotype, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Genetic Linkage