Objective To assess if a coding variant in the gene encoding transient receptor potential cation channel, subfamily V, member 1 (TRPV1) is associated with genetic risk of painful knee osteoarthritis (OA).
Methods The Ile585Val TRPV1 variant encoded by rs8065080 was genotyped in 3270 cases of symptomatic knee OA, 1098 cases of asymptomatic knee OA and 3852 controls from seven cohorts from the UK, the USA and Australia. The genetic association between the low-pain genotype Ile–Ile and risk of symptomatic and asymptomatic knee OA was assessed.
Results The TRPV1 585 Ile–Ile genotype, reported to be associated with lower thermal pain sensitivity, was associated with a lower risk of symptomatic knee OA in a comparison of symptomatic cases with healthy controls, with an odds ratio (OR) of 0.75 (95% CI 0.64 to 0.88; p=0.00039 by meta-analysis) after adjustment for age, sex and body mass index. No difference was seen between asymptomatic OA cases and controls (OR=1.02, 95% CI 0.82 to 1.27 p=0.86) but the Ile–Ile genotype was associated with lower risk of symptomatic versus asymptomatic knee OA adjusting for covariates and radiographic severity (OR=0.73, 95% CI 0.57 to 0.94 p=0.0136). TRPV1 expression in articular cartilage was increased by inflammatory cytokines (tumour necrosis factor α and interleukin 1). However, there were no differences in TRPV1 expression in healthy and arthritic synovial tissue.
Conclusions A genotype involved in lower peripheral pain sensitivity is significantly associated with a decreased risk of painful knee OA. This indicates a role for the pro-nociceptive gene TRPV1 in genetic susceptibility to symptomatic knee OA, which may also be influenced by a role for this molecule in cartilage function.
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NKA and MD contributed equally
Funding Supported by EC-FP7 programme grant 200800 TREAT-OA. AstraZeneca UK funded the GOAL study sample and data collection. The TwinsUK cohort is funded by the Wellcome Trust. The Hertfordshire Cohort Study (HCS) is supported by the Medical Research Council (UK) and the Oxford NIHR Musculoskeletal Biomedical Research Unit. The Clearwater Osteoarthritis Study has been funded by private donations. The Arthritis Research Campaign provided infrastructure support during the GOAL study, the collection of the Nottingham case–control study and for the Chingford Study and HCS. The Tasmanian Older Adult Cohort collection was funded by the National Health and Medical Research Council of Australia, Arthritis Foundation of Australia; Tasmanian Community Fund and a University of Tasmania Grant-Institutional Research Scheme.
Competing interest Dr. RA Maciewicz is employed by, owns stock and has patent applications for AstraZeneca. All other authors and organizations declare no conflict of interest.
Ethics approval This study was conducted with the approval of the Guy's and St Thomas' Trust and the Waltham Forest Trust ethics committees, research ethics committees of Nottingham City Hospital and North Nottinghamshire, East and North Hertfordshire ethical committees.
Provenance and peer review Not commissioned; externally peer reviewed.
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