Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain.
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(V)1.7. METHODS: Knee OA patients from 2 UK cohorts (1,411 from the Genetics of Osteoart...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2011
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| _version_ | 1797090825749921792 |
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| author | Valdes, A Arden, N Vaughn, F Doherty, SA Leaverton, P Zhang, W Muir, K Rampersaud, E Dennison, E Edwards, M Jameson, K Javaid, M Spector, T Cooper, C Maciewicz, R Doherty, M |
| author_facet | Valdes, A Arden, N Vaughn, F Doherty, SA Leaverton, P Zhang, W Muir, K Rampersaud, E Dennison, E Edwards, M Jameson, K Javaid, M Spector, T Cooper, C Maciewicz, R Doherty, M |
| author_sort | Valdes, A |
| collection | OXFORD |
| description | 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(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 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(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. |
| first_indexed | 2024-03-07T03:24:18Z |
| format | Journal article |
| id | oxford-uuid:b881a5df-36d5-420f-8cca-d9ea9cf02c7d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:24:18Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:b881a5df-36d5-420f-8cca-d9ea9cf02c7d2022-03-27T04:56:23ZRole of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b881a5df-36d5-420f-8cca-d9ea9cf02c7dEnglishSymplectic Elements at Oxford2011Valdes, AArden, NVaughn, FDoherty, SALeaverton, PZhang, WMuir, KRampersaud, EDennison, EEdwards, MJameson, KJavaid, MSpector, TCooper, CMaciewicz, RDoherty, MOBJECTIVE: 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. 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(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. |
| spellingShingle | Valdes, A Arden, N Vaughn, F Doherty, SA Leaverton, P Zhang, W Muir, K Rampersaud, E Dennison, E Edwards, M Jameson, K Javaid, M Spector, T Cooper, C Maciewicz, R Doherty, M Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain. |
| title | Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain. |
| title_full | Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain. |
| title_fullStr | Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain. |
| title_full_unstemmed | Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain. |
| title_short | Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain. |
| title_sort | role of the nav1 7 r1150w amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain |
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