Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain
| Autor: | Frances L. Vaughn, Rose A. Maciewicz, Mark H. Edwards, Michael Doherty, Tim D. Spector, Ana M. Valdes, Karen A. Jameson, Evandine Rampersaud, Nigel K Arden, Sally Doherty, M Kassim Javaid, Weiya Zhang, Elaine M. Dennison, Paul E. Leaverton, Kenneth Muir, Cyrus Cooper |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
medicine.medical_specialty WOMAC Osteoarthritis Risk Assessment Severity of Illness Index Asymptomatic Sodium Channels 03 medical and health sciences 0302 clinical medicine Gene Frequency Rheumatology Risk Factors Internal medicine Severity of illness Arthropathy Odds Ratio Humans Medicine Genetic Predisposition to Disease Aged Pain Measurement Aged 80 and over 030203 arthritis & rheumatology business.industry NAV1.7 Voltage-Gated Sodium Channel Odds ratio Middle Aged Osteoarthritis Knee medicine.disease United Kingdom United States 3. Good health Radiography Logistic Models Phenotype Amino Acid Substitution Mutation Linear Models Physical therapy Female medicine.symptom business Complex Regional Pain Syndromes 030217 neurology & neurosurgery Cohort study |
| Zdroj: | Arthritis Care & Research; Vol |
| Popis: | Objective: to assess the genetic association of pain in patients with knee osteoarthritis (OA) and those with multiple regional pain with the R1150W variant in the ?-subunit of the voltage-gated sodium channel Na(V)1.7. Methods: knee OA patients from 2 UK cohorts (1,411 from the Genetics of Osteoarthritis and Lifestyle study and 267 from the Hertfordshire Cohort Study; 74% with symptomatic OA) with Western Ontario and McMaster Universities OA Index (WOMAC) pain scores were genotyped for rs6746030 (encoding the R1150W change). One hundred seventy-six knee OA patients (53% symptomatic) from the Clearwater Osteoarthritis Study were also tested. A total of 4,295 samples (both affected and unaffected OA) from all 3 studies with data on multiple regional pain were tested. Fixed-effects meta-analyses were carried out with the WOMAC, symptomatic OA (adjusting for radiographic severity), and multiple regional pain as outcomes. Results: no association with the WOMAC was seen in the UK cohorts. Overall, the meta-analysis of WOMAC yielded a summary statistic of ? = 0.47 (95% confidence interval [95% CI] 0.04, 0.89; P = 0.030) for the variant allele. The meta-analysis of symptomatic versus asymptomatic OA did not demonstrate an association with rs6746030 (odds ratio [OR] 0.90 [95% CI 0.71, 1.15], P = 0.38). The meta-analysis of multiple regional pain resulted in a significant OR of 1.40 (95% CI 1.08, 1.80; P = 0.0085). No interstudy heterogeneity was seen for any of the analyses. Conclusion: we find evidence that the R1150W amino acid change in the Na(V)1.7 ?-chain is associated with multiple regional pain. This variant is confirmed to be involved in genetic susceptibility to pain, but it does not appear to have a major role in OA-specific pain |
| Databáze: | OpenAIRE |
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