University of Tasmania
Browse

File(s) under permanent embargo

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

journal contribution
posted on 2023-05-17, 10:45 authored by Valdes, AM, De Wilde, G, Doherty, SA, Lories, RJ, Vaughn, FL, Laura LaslettLaura Laslett, Maciewicz, RA, Soni, A, Hart, DJ, Zhang, W, Muir, KR, Dennison, EM, Wheeler, M, Leaverton, P, Cooper, C, Spector, TD, Cicuttini, FM, Chapman, V, Graeme JonesGraeme Jones, Arden, NK, Doherty, M
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.

History

Publication title

Annals of The Rheumatic Diseases: The Eular Journal

Volume

70

Issue

9

Pagination

1556-1561

ISSN

0003-4967

Department/School

Menzies Institute for Medical Research

Publisher

B M J Publishing Group

Place of publication

British Med Assoc House, Tavistock Square, London, England, Wc1H 9Jr

Rights statement

Copyright © 2011 BMJ Publishing

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

Usage metrics

    University Of Tasmania

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC