. (2011) The Ile585Val TRPV1 variant is involved in risk of painful knee osteoarthritis. Annals of the Rheumatic Diseases, Vol.70 (No.9). pp. 1556-1561. ISSN 0003-4967

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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 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 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 Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine
Divisions:	Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Osteoarthritis -- Genetic aspects, Knee -- Diseases -- Genetic aspects
Journal or Publication Title:	Annals of the Rheumatic Diseases
Publisher:	BMJ Group
ISSN:	0003-4967
Date:	25 May 2011
Volume:	Vol.70
Number:	No.9
Page Range:	pp. 1556-1561
Identification Number:	10.1136/ard.2010.148122
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	Seventh Framework Programme (European Commission) (FP7/2007-2013), AstraZeneca (Firm), Wellcome Trust (London, England), Medical Research Council (Great Britain) (MRC), National Institute for Health Research (Great Britain) (NIHR), Arthritis Research Campaign (Organization), National Health and Medical Research Council (Australia) (NHMRC), Arthritis Foundation of Australia, Tasmanian Community Fund, University of Tasmania
Grant number:	200800 TREAT-OA (FP7)
References:	1. Lopez AD, Mathers CD, Ezzati M, et al. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 2006 ; 367 : 1747 – 57 . 2. Pincus T, Block JA. Pain and radiographic damage in osteoarthritis. B MJ 2009 ; 339 : b2802 . 3. Duncan R, Peat G, Thomas E, et al. Symptoms and radiographic osteoarthritis: not as discordant as they are made out to be? Ann Rheum Dis 2007 ; 66 : 86 – 91 . 4. Felson DT, Naimark A, Anderson J, et al. The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum 1987 ; 30 : 914 – 18 . 5. Lethbridge-Cejku M, Scott WW, Jr , Reichle R, et al. Association of radiographic features of osteoarthritis of the knee with knee pain: data from the Baltimore Longitudinal Study of Aging. Arthritis Care Res 1995 ; 8 : 182 – 8 . 6. Foulkes T, Wood JN. Pain genes. PLoS Genet 2008 ; 4 : e1000086 . 7. Caterina MJ, Rosen TA, Tominaga M, et al. A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 1999 ; 398 : 436 – 41 . 8. Basbaum AI, Bautista DM, Scherrer G, et al. Cellular and molecular mechanisms of pain. Cell 2009 ; 139 : 267 – 84 . 9. Huang J, Zhang X, McNaughton PA. Infl ammatory pain: the cellular basis of heat hyperalgesia. Curr Neuropharmacol 2006 ; 4 : 197 – 206 . 10. Fernihough J, Gentry C, Bevan S, et al. Regulation of calcitonin generelated peptide and TRPV1 in a rat model of osteoarthritis. Neurosci Lett 2005 ; 388 : 75 – 80 . 11. Chu KL, Chandran P, Joshi SK, et al. TRPV1-related modulation of spinal neuronal activity and behavior in a rat model of osteoarthritic pain. Brain Res 2011 ; 1369 : 158 – 66 . 12. Gavenis K, Schumacher C, Schneider U, et al. Expression of ion channels of the TRP family in articular chondrocytes from osteoarthritic patients: changes between native and i n vitro propagated chondrocytes. M ol Cell Biochem 2009 ; 321 : 135 – 43. 13. Idris AI, Landao-Bassonga E, Ralston SH. The TRPV1 ion channel antagonist capsazepine inhibits osteoclast and osteoblast differentiation in vitro and ovariectomy induced bone loss in vivo. Bone 2010 ; 46 : 1089 – 99 . 14. Engler A, Aeschlimann A, Simmen BR, et al. Expression of transient receptor potential vanilloid 1 (TRPV1) in synovial fi broblasts from patients with osteoarthritis and rheumatoid arthritis. Biochem Biophys Res Commun 2007 ; 359 : 884– 8. 15. Kim H, Neubert JK, San Miguel A, et al. Genetic infl uence on variability in human acute experimental pain sensitivity associated with gender, ethnicity and psychological temperament. Pain 2004 ; 109 : 488 – 96 . 16. Lötsch J, Flühr K, Neddermayer T, et al. The consequence of concomitantly present functional genetic variants for the identifi cation of functional genotype-phenotype associations in pain. Clin Pharmacol Ther 2009 ; 85 : 25 – 30 . 17. Altman RD, Hochberg M, Murphy WA, Jr , et al. Atlas of individual radiographic features in osteoarthritis. Osteoarthr Cartil 1995 ; 3 Suppl A : 3 – 70 . 18. Lories RJ, Derese I, De Bari C, et al. In vitro growth rate of fi broblast-like synovial cells is reduced by methotrexate treatment. Ann Rheum Dis 2003 ; 62 : 568 – 71 . 19. Willems E, Leyns L, Vandesompele J. Standardization of real-time PCR gene expression data from independent biological replicates. Anal Biochem 2008 ; 379 : 127 – 9 . 20. Kochukov MY, McNearney TA, Yin H, et al. Tumor necrosis factor-alpha (TNF-alpha) enhances functional thermal and chemical responses of TRP cation channels in human synoviocytes. Mol Pain 2009 ; 5 : 49 . 21. Valdes AM, Spector TD, Doherty S, et al. Association of the DVWA and GDF5 polymorphisms with osteoarthritis in UK populations. Ann Rheum Dis 2009 ; 68 : 1916 – 20 . 22. Valdes AM, Spector TD. The clinical relevance of genetic susceptibility to osteoarthritis. Best Pract Res Clin Rheumatol 2010 ; 24 : 3 – 14 . 23. Neogi T, Felson D, Niu J, et al. Association between radiographic features of knee osteoarthritis and pain: results from two cohort studies. BMJ 2009 ; 339 : b2844 . 24. Lundblad H, Kreicbergs A. Jansson KA . Prediction of persistent pain after total knee replacement for osteoarthritis . J Bone Joint Surg Br 2008;90:166–71. 25. Zhang W, Nuki G, Moskowitz RW, et al. OARSI recommendations for the management of hip and knee osteoarthritis: part III: Changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthr Cartil 2010 ; 18 : 476 – 99 . 26. Puttfarcken PS, Han P, Joshi SK, e t al. A-995662 [®-8-(4-methyl-5-(4- (trifl uoromethyl)phenyl)oxazol-2-ylamino)-1,2,3,4-tetrahydronaphthalen-2-ol], a novel, selective TRPV1 receptor antagonist, reduces spinal release of glutamate and CGRP in a rat knee joint pain model. Pain 2010 ; 150 : 319 – 26 . 27. Kalff KM, El Mouedden M, van Egmond J, et al. Pre-treatment with capsaicin in a rat osteoarthritis model reduces the symptoms of pain and bone damage induced by monosodium iodoacetate. Eur J Pharmacol 2010 ; 641 : 108 – 13 . 28. Schaible HG, von Banchet GS, Boettger MK, et al. The role of proinfl ammatory cytokines in the generation and maintenance of joint pain. Ann N Y Acad Sci 2010 ; 1193 : 60 – 9 . 29. Saunders J, Ding C, Cicuttini F, et al. Radiographic osteoarthritis and pain are independent predictors of knee cartilage loss: a prospective study. Intern Med J 2011 ;Published Online First: 8 Feb 2011. doi:10.1111/j.1445-5994.2011.02438.x. 30. Hu F, Sun WW, Zhao XT, et al. TRPV1 mediates cell death in rat synovial fi broblasts through calcium entry-dependent ROS production and mitochondrial depolarization. Biochem Biophys Res Commun 2008 ; 369 : 989 – 93 . 31. Medical News Today, July 2010. http://www.medicalnewstoday.com/ articles/195482.php (accessed 20 April 2011).
URI:	http://wrap.warwick.ac.uk/id/eprint/36900

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