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The Ile585Val TRPV1 variant is involved in risk of painful knee osteoarthritis


Valdes, AM and De Wilde, G and Doherty, SA and Lories, RJ and Vaughn, FL and Laslett, LL and Maciewicz, RA and Soni, A and Hart, DJ and Zhang, W and Muir, KR and Dennison, EM and Wheeler, M and Leaverton, P and Cooper, C and Spector, TD and Cicuttini, FM and Chapman, V and Jones, G and Arden, NK and Doherty, M, The Ile585Val TRPV1 variant is involved in risk of painful knee osteoarthritis, Annals of The Rheumatic Diseases: The Eular Journal, 70, (9) pp. 1556-1561. ISSN 0003-4967 (2011) [Refereed Article]

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Copyright © 2011 BMJ Publishing

DOI: doi:10.1136/ard.2010.148122


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 infl ammatory cytokines (tumour necrosis factor á 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 signifi cantly 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 infl uenced by a role for this molecule in cartilage function.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Rheumatology and arthritis
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Laslett, LL (Dr Laura Laslett)
UTAS Author:Jones, G (Professor Graeme Jones)
ID Code:76230
Year Published:2011
Web of Science® Times Cited:84
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-03-02
Last Modified:2012-04-03

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