The Ile585Val TRPV1 variant is involved in risk of painful knee osteoarthritis
| Autor: | Elaine M. Dennison, Rik Lories, Cyrus Cooper, Weiya Zhang, Margaret Wheeler, Deborah J. Hart, Sally Doherty, Victoria Chapman, Ana M. Valdes, Gert De Wilde, Tim D. Spector, Graeme Jones, Paul E. Leaverton, Nigel K Arden, Frances L. Vaughn, Laura L Laslett, Rose A. Maciewicz, Michael Doherty, Flavia M. Cicuttini, Kenneth Muir, Anushka Soni |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Cartilage
Articular Male medicine.medical_specialty Genotype Immunology Pain TRPV Cation Channels Osteoarthritis Lower risk Asymptomatic Gastroenterology General Biochemistry Genetics and Molecular Biology Tissue Culture Techniques 03 medical and health sciences 0302 clinical medicine Rheumatology Gene Frequency Internal medicine Genetic predisposition Immunology and Allergy Medicine Humans Genetic Predisposition to Disease QH426 Aged 030203 arthritis & rheumatology 2. Zero hunger business.industry Case-control study Genetic Variation Odds ratio Middle Aged Osteoarthritis Knee Clinical and Epidemiological Research medicine.disease 3. Good health Surgery Case-Control Studies Female medicine.symptom business Body mass index 030217 neurology & neurosurgery RC |
| Zdroj: | Annals of the Rheumatic Diseases Annals of the Rheumatic Diseases; Vol 70 |
| ISSN: | 0003-4967 |
| Popis: | Objective To assess if a coding variant in the gene\ud encoding transient receptor potential cation channel,\ud subfamily V, member 1 ( TRPV1 ) is associated with\ud genetic risk of painful knee osteoarthritis (OA).\ud Methods The Ile585Val TRPV1 variant encoded by\ud rs8065080 was genotyped in 3270 cases of symptomatic\ud knee OA, 1098 cases of asymptomatic knee OA and\ud 3852 controls from seven cohorts from the UK, the USA\ud and Australia. The genetic association between the\ud low-pain genotype Ile–Ile and risk of symptomatic and\ud asymptomatic knee OA was assessed.\ud Results The TRPV1 585 Ile–Ile genotype, reported to\ud be associated with lower thermal pain sensitivity, was\ud associated with a lower risk of symptomatic knee OA\ud in a comparison of symptomatic cases with healthy\ud controls, with an odds ratio (OR) of 0.75 (95% CI 0.64\ud to 0.88; p=0.00039 by meta-analysis) after adjustment\ud for age, sex and body mass index. No difference was\ud seen between asymptomatic OA cases and controls\ud (OR=1.02, 95% CI 0.82 to 1.27 p=0.86) but the Ile–Ile\ud genotype was associated with lower risk of symptomatic\ud versus asymptomatic knee OA adjusting for covariates\ud and radiographic severity (OR=0.73, 95% CI 0.57 to 0.94\ud p=0.0136). TRPV1 expression in articular cartilage was\ud increased by infl ammatory cytokines (tumour necrosis\ud factor α and interleukin 1). However, there were no\ud differences in TRPV1 expression in healthy and arthritic\ud synovial tissue.\ud Conclusions A genotype involved in lower peripheral\ud pain sensitivity is signifi cantly associated with a\ud decreased risk of painful knee OA. This indicates a role for\ud the pro-nociceptive gene TRPV1 in genetic susceptibility\ud to symptomatic knee OA, which may also be infl uenced\ud by a role for this molecule in cartilage function. |
| Databáze: | OpenAIRE |
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