Role of the Na v1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain

Ana M. Valdes, Nigel K. Arden, Frances L. Vaughn, Sally A. Doherty, Paul E. Leaverton, Weiya Zhang, Kenneth R. Muir, Evadnie Rampersaud, Elaine M. Dennison, Mark H. Edwards, Karen A. Jameson, M. Kassim Javaid, Tim D. Spector, Cyrus Cooper, Rose A. MacIewicz, Michael Doherty

Research output: Contribution to journalArticle

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Abstract

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 α-subunit of the voltage-gated sodium channel Na V1.7. 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 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. Conclusion. We find evidence that the R1150W amino acid change in the Na V1.7 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.

Original languageEnglish
Pages (from-to)440-444
Number of pages5
JournalArthritis Care and Research
Volume63
Issue number3
DOIs
StatePublished - Mar 1 2011

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Knee Osteoarthritis
Osteoarthritis
Amino Acids
Pain
Meta-Analysis
Confidence Intervals
Odds Ratio
Voltage-Gated Sodium Channels
Ontario
Genetic Predisposition to Disease
Life Style
Cohort Studies
Alleles

ASJC Scopus subject areas

  • Rheumatology
  • Medicine(all)

Cite this

Valdes, A. M., Arden, N. K., Vaughn, F. L., Doherty, S. A., Leaverton, P. E., Zhang, W., ... Doherty, M. (2011). Role of the Na v1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain. Arthritis Care and Research, 63(3), 440-444. https://doi.org/10.1002/acr.20375

Role of the Na v1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain. / 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.

In: Arthritis Care and Research, Vol. 63, No. 3, 01.03.2011, p. 440-444.

Research output: Contribution to journalArticle

Valdes, AM, Arden, NK, Vaughn, FL, Doherty, SA, Leaverton, PE, Zhang, W, Muir, KR, Rampersaud, E, Dennison, EM, Edwards, MH, Jameson, KA, Javaid, MK, Spector, TD, Cooper, C, MacIewicz, RA & Doherty, M 2011, 'Role of the Na v1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain', Arthritis Care and Research, vol. 63, no. 3, pp. 440-444. https://doi.org/10.1002/acr.20375
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. / Role of the Na v1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain. In: Arthritis Care and Research. 2011 ; Vol. 63, No. 3. pp. 440-444.
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AU - Valdes, Ana M.

AU - Arden, Nigel K.

AU - Vaughn, Frances L.

AU - Doherty, Sally A.

AU - Leaverton, Paul E.

AU - Zhang, Weiya

AU - Muir, Kenneth R.

AU - Rampersaud, Evadnie

AU - Dennison, Elaine M.

AU - Edwards, Mark H.

AU - Jameson, Karen A.

AU - Javaid, M. Kassim

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AB - 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 α-subunit of the voltage-gated sodium channel Na V1.7. 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 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. Conclusion. We find evidence that the R1150W amino acid change in the Na V1.7 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.

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