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- Title
Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain.
- Authors
Valdes, Ana M.; Arden, Nigel K.; Vaughn, Frances L.; Doherty, Sally A.; Leaverton, Paul E.; Zhang, Weiya; Muir, Kenneth R.; Rampersaud, Evadnie; Dennison, Elaine M.; Edwards, Mark H.; Jameson, Karen A.; Javaid, M. Kassim; Spector, Tim D.; Cooper, Cyrus; Maciewicz, Rose A.; Doherty, Michael
- Abstract
<bold>Objective: </bold>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 α-subunit of the voltage-gated sodium channel Na(V)1.7.<bold>Methods: </bold>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.<bold>Results: </bold>No association with the WOMAC was seen in the UK cohorts. Overall, the meta-analysis of WOMAC yielded a summary statistic of β = 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.<bold>Conclusion: </bold>We find evidence that the R1150W amino acid change in the Na(V)1.7 α-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.
- Publication
Arthritis Care & Research, 2011, Vol 63, Issue 3, p440
- ISSN
2151-464X
- Publication type
journal article
- DOI
10.1002/acr.20375