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The lle5858Val TRPV1 variant is involved in risk of painful knee osteoarthritis

The lle5858Val TRPV1 variant is involved in risk of painful knee osteoarthritis
The lle5858Val TRPV1 variant is involved in risk of painful knee osteoarthritis
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 ? 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
0003-4967
1556-1561
Valdes, Ana M.
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De Wilde, Gert
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Doherty, Sally A.
a28bef1a-01a7-4c85-8e91-49afba4f923a
Lories, Rik J.
8592bc0a-34de-4095-a33d-6045af07ef50
Vaughn, Frances L.
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Laslett, Laura L.
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Maciewicz, Rose A.
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Soni, Anushka
5b9827c7-be82-42cf-b7d3-707d73c6da5a
Hart, Deborah J.
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Zhang, Weiya
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Muir, Kenneth R.
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Dennison, Elaine M.
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Wheeler, Margaret
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Leaverton, Paul
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Cooper, Cyrus
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Spector, Tim D.
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Cicuttini, Flavia M.
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Chapman, Victoria
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Jones, Graeme
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Arden, Nigel K.
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Doherty, Michael
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Valdes, Ana M.
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De Wilde, Gert
e3beeac8-baf4-47e3-b24e-0cc0b1f7a302
Doherty, Sally A.
a28bef1a-01a7-4c85-8e91-49afba4f923a
Lories, Rik J.
8592bc0a-34de-4095-a33d-6045af07ef50
Vaughn, Frances L.
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Laslett, Laura L.
1eb34fd0-ba43-4f1e-8357-449d747a53a1
Maciewicz, Rose A.
c33d1ff0-a737-472e-9f30-ad5ac6bafa28
Soni, Anushka
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Hart, Deborah J.
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Zhang, Weiya
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Muir, Kenneth R.
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Dennison, Elaine M.
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Wheeler, Margaret
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Leaverton, Paul
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Cooper, Cyrus
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Spector, Tim D.
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Cicuttini, Flavia M.
f6ba6cd6-164e-40ca-845b-2c4d9e188831
Chapman, Victoria
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Jones, Graeme
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Arden, Nigel K.
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Doherty, Michael
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Valdes, Ana M., De Wilde, Gert, Doherty, Sally A., Lories, Rik J., Vaughn, Frances L., Laslett, Laura L., Maciewicz, Rose A., Soni, Anushka, Hart, Deborah J., Zhang, Weiya, Muir, Kenneth R., Dennison, Elaine M., Wheeler, Margaret, Leaverton, Paul, Cooper, Cyrus, Spector, Tim D., Cicuttini, Flavia M., Chapman, Victoria, Jones, Graeme, Arden, Nigel K. and Doherty, Michael (2011) The lle5858Val TRPV1 variant is involved in risk of painful knee osteoarthritis. Annals of the Rheumatic Diseases, 70 (9), 1556-1561. (doi:10.1136/ard.2010.148122). (PMID:21616913)

Record type: Article

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 inflammatory cytokines (tumour necrosis factor ? 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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Published date: September 2011
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 194759
URI: http://eprints.soton.ac.uk/id/eprint/194759
ISSN: 0003-4967
PURE UUID: cafb25d6-462e-4091-9319-d37332b36fb2
ORCID for Elaine M. Dennison: ORCID iD orcid.org/0000-0002-3048-4961
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 10 Aug 2011 11:04
Last modified: 18 Feb 2021 16:48

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Contributors

Author: Ana M. Valdes
Author: Gert De Wilde
Author: Sally A. Doherty
Author: Rik J. Lories
Author: Frances L. Vaughn
Author: Laura L. Laslett
Author: Rose A. Maciewicz
Author: Anushka Soni
Author: Deborah J. Hart
Author: Weiya Zhang
Author: Kenneth R. Muir
Author: Margaret Wheeler
Author: Paul Leaverton
Author: Cyrus Cooper ORCID iD
Author: Tim D. Spector
Author: Flavia M. Cicuttini
Author: Victoria Chapman
Author: Graeme Jones
Author: Nigel K. Arden
Author: Michael Doherty

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