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Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain

Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain
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 ?-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
0004-3591
440-444
Valdes, Ana M.
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Arden, Nigel K.
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Vaughn, Frances L.
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Doherty, Sally A.
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Leaverton, Paul E.
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Zhang, Weiya
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Muir, Kenneth R.
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Rampersaud, Evandine
a1d8a6ca-8bfd-4330-85f1-ce435ddddbbe
Dennison, Elaine M.
ee647287-edb4-4392-8361-e59fd505b1d1
Edwards, Mark H.
b81ff294-1d16-4a1b-af14-9374c5989d4c
Jameson, Karen A.
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Javaid, M. Kassim
64155236-2ef0-4065-b684-cf723a888117
Spector, Tim D.
1e47066c-6620-4f86-af6f-89d9e130ffc2
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Maciewicz, Rose A.
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Doherty, Michael
ab3e38b1-4e66-48b0-ae34-ec710c4fce2c
Valdes, Ana M.
4e4c3f14-3895-4129-94ca-f4176dd83e94
Arden, Nigel K.
23af958d-835c-4d79-be54-4bbe4c68077f
Vaughn, Frances L.
b210208c-001a-4389-84b8-6f8a9d52eabf
Doherty, Sally A.
a28bef1a-01a7-4c85-8e91-49afba4f923a
Leaverton, Paul E.
36a95f21-a4e3-4b36-aac4-774e317f5f35
Zhang, Weiya
55a653cf-e6e5-4103-bae1-8f92f3855d6e
Muir, Kenneth R.
4703d677-d4f5-4386-aa1e-2de40e31354f
Rampersaud, Evandine
a1d8a6ca-8bfd-4330-85f1-ce435ddddbbe
Dennison, Elaine M.
ee647287-edb4-4392-8361-e59fd505b1d1
Edwards, Mark H.
b81ff294-1d16-4a1b-af14-9374c5989d4c
Jameson, Karen A.
d5fb142d-06af-456e-9016-17497f94e9f2
Javaid, M. Kassim
64155236-2ef0-4065-b684-cf723a888117
Spector, Tim D.
1e47066c-6620-4f86-af6f-89d9e130ffc2
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Maciewicz, Rose A.
c33d1ff0-a737-472e-9f30-ad5ac6bafa28
Doherty, Michael
ab3e38b1-4e66-48b0-ae34-ec710c4fce2c

Valdes, Ana M., Arden, Nigel K., Vaughn, Frances L., Doherty, Sally A., Leaverton, Paul E., Zhang, Weiya, Muir, Kenneth R., Rampersaud, Evandine, Dennison, Elaine M., Edwards, Mark H., Jameson, Karen A., Javaid, M. Kassim, Spector, Tim D., Cooper, Cyrus, Maciewicz, Rose A. and Doherty, Michael (2011) Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain. Arthritis & Rheumatism, 63 (3), 440-444. (doi:10.1002/acr.20375). (PMID:21031562)

Record type: Article

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 ?-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

Full text not available from this repository.

More information

e-pub ahead of print date: 25 February 2011
Published date: March 2011
Organisations: Faculty of Medicine, Faculty of Health Sciences

Identifiers

Local EPrints ID: 336989
URI: http://eprints.soton.ac.uk/id/eprint/336989
ISSN: 0004-3591
PURE UUID: fbf1b6c0-aaaa-4f7c-b007-bdfed2ee508f
ORCID for Elaine M. Dennison: ORCID iD orcid.org/0000-0002-3048-4961
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

Catalogue record

Date deposited: 13 Apr 2012 07:30
Last modified: 18 Feb 2021 16:48

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