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The Ile585Val TRPV1 variant is involved in risk of painful knee osteoarthritis
Citation
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 Statement
Copyright © 2011 BMJ Publishing
DOI: doi:10.1136/ard.2010.148122
Abstract
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: | Medical and Health Sciences |
| Research Group: | Clinical Sciences |
| Research Field: | Rheumatology and Arthritis |
| Objective Division: | Health |
| Objective Group: | Clinical Health (Organs, Diseases and Abnormal Conditions) |
| Objective Field: | Skeletal System and Disorders (incl. Arthritis) |
| Author: | Laslett, LL (Dr Laura Laslett) |
| Author: | Jones, G (Professor Graeme Jones) |
| ID Code: | 76230 |
| Year Published: | 2011 |
| Web of Science® Times Cited: | 61 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2012-03-02 |
| Last Modified: | 2012-04-03 |
| Downloads: | 0 |
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