Role of the Na(V)1.7 R1150W Amino Acid Change in Susceptibility to Symptomatic Knee Osteoarthritis and Multiple Regional Pain

TY - JOUR

T1 - Role of the Na(V)1.7 R1150W Amino Acid Change in Susceptibility to Symptomatic Knee Osteoarthritis and Multiple Regional Pain

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

AU - Spector, Tim D.

AU - Cooper, Cyrus

AU - Maciewicz, Rose A.

AU - Doherty, Michael

PY - 2011/3

Y1 - 2011/3

N2 - 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 alpha-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 beta = 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 alpha-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.

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 alpha-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 beta = 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 alpha-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.

U2 - 10.1002/acr.20375

DO - 10.1002/acr.20375

M3 - Article

VL - 63

SP - 440

EP - 444

JO - ARTHRITIS CARE AND RESEARCH

JF - ARTHRITIS CARE AND RESEARCH

IS - 3

ER -