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The non-synonymous SNP, R1150W, in SCN9A is not associated with chronic widespread pain susceptibility

The non-synonymous SNP, R1150W, in SCN9A is not associated with chronic widespread pain susceptibility
The non-synonymous SNP, R1150W, in SCN9A is not associated with chronic widespread pain susceptibility

Background: Mutations in SCN9A, encoding the alpha subunit of the voltage-gated sodium channel (Nav1.7), have caused severe pain disorders and congenital insensitivity to pain. The aim of this study was to validate the previously reported association between a common non-synonymous polymorphism (R1150W, rs6746030) in SCN9A and chronic widespread pain (CWP), in independent population-based cohorts.Findings: Genotype data for rs6746030 was available in four population-based cohorts (EPIFUND, the European Male Ageing Study (EMAS), the Framingham study and the Dyne Steel DNA Bank of Ageing and Cognition). Pain was assessed using body manikins and CWP was scored using American College of Rheumatology (ACR) criteria in all cohorts, except the Framingham study which assessed widespread pain (WP) using ACR criteria on a joint pain homunculus. Controls were subjects who reported no pain. Logistic regression (additive genetic model) was used to test for association between rs6746030 and CWP compared to controls, adjusting for study centre in EMAS. Generalised estimating equation regression was used to test for association between rs6746030 and WP, whilst accounting for relatedness between subjects in the Framingham study.Genotype data for rs6746030 was available for 1071 CWP cases and 3212 controls. There was no significant association between CWP and rs6476030 in individual cohorts or when combined in a fixed-effects meta-analysis (Odds Ratio = 0.96 (95% confidence interval 0.82, 1.11) p = 0.567).Conclusions: In contrast to a previous study, no association between a non-synonymous polymorphism in SCN9A and CWP was observed in multiple population-based cohorts.

Chronic widespread pain, Population-based cohorts, Single nucleotide polymorphism, Voltage-gated sodium channel
1744-8069
Holliday, Kate L.
58c01428-143a-4fc8-bd97-eb513573a697
Thomson, Wendy
137a22b9-79fc-4689-bc21-a7c2901cd8d7
Neogi, Tuhina
e608f8b8-b0e7-4bb2-a190-68466b81d066
Felson, David T.
72acd3b2-3731-47b7-b961-88d3c408eb42
Wang, Ke
60aeff7b-b4c0-4b9d-8803-4578fd7ddef3
Wu, Frederick C.
b3fa3b4a-7ba3-411b-a4e8-59536d64b304
Huhtaniemi, Ilpo T.
44b7325c-b07b-43c2-8637-a815cb437f0b
Bartfai, Gyorgy
44b43d57-f9a9-43a4-b804-345281d7f65f
Casanueva, Felipe
f5ed3d8c-09ae-423a-9e3b-a8a0700fadb6
Forti, Gianni
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Kula, Krzysztof
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Punab, Margus
bbd616cf-73e3-4845-b644-588b133558f2
Vanderschueren, Dirk
f705ade5-7105-4fd7-8d74-17e4f8b7f32c
Macfarlane, Gary J.
e17bbdb7-9d82-42ac-8a0a-09bf10885e3c
Horan, Michael A.
ed25c30d-2dcf-4ea2-ae7d-d2f4040156f8
Ollier, William
36ca1aa8-617b-45d6-b972-b345f718129f
Payton, Antony
eedef58d-bd8b-4adb-b8d1-6b444bbf66ab
Pendleton, Neil
d53e2dab-7691-4b35-96a9-1a2922e61033
McBeth, John
98012716-66ba-480b-9e43-ac53b51dce61
Holliday, Kate L.
58c01428-143a-4fc8-bd97-eb513573a697
Thomson, Wendy
137a22b9-79fc-4689-bc21-a7c2901cd8d7
Neogi, Tuhina
e608f8b8-b0e7-4bb2-a190-68466b81d066
Felson, David T.
72acd3b2-3731-47b7-b961-88d3c408eb42
Wang, Ke
60aeff7b-b4c0-4b9d-8803-4578fd7ddef3
Wu, Frederick C.
b3fa3b4a-7ba3-411b-a4e8-59536d64b304
Huhtaniemi, Ilpo T.
44b7325c-b07b-43c2-8637-a815cb437f0b
Bartfai, Gyorgy
44b43d57-f9a9-43a4-b804-345281d7f65f
Casanueva, Felipe
f5ed3d8c-09ae-423a-9e3b-a8a0700fadb6
Forti, Gianni
9a44a93a-2ac6-4f74-a681-2d1331d352b7
Kula, Krzysztof
9d9d4ce5-7d2b-4ee3-a9a0-7396c6d24e45
Punab, Margus
bbd616cf-73e3-4845-b644-588b133558f2
Vanderschueren, Dirk
f705ade5-7105-4fd7-8d74-17e4f8b7f32c
Macfarlane, Gary J.
e17bbdb7-9d82-42ac-8a0a-09bf10885e3c
Horan, Michael A.
ed25c30d-2dcf-4ea2-ae7d-d2f4040156f8
Ollier, William
36ca1aa8-617b-45d6-b972-b345f718129f
Payton, Antony
eedef58d-bd8b-4adb-b8d1-6b444bbf66ab
Pendleton, Neil
d53e2dab-7691-4b35-96a9-1a2922e61033
McBeth, John
98012716-66ba-480b-9e43-ac53b51dce61

Holliday, Kate L., Thomson, Wendy, Neogi, Tuhina, Felson, David T., Wang, Ke, Wu, Frederick C., Huhtaniemi, Ilpo T., Bartfai, Gyorgy, Casanueva, Felipe, Forti, Gianni, Kula, Krzysztof, Punab, Margus, Vanderschueren, Dirk, Macfarlane, Gary J., Horan, Michael A., Ollier, William, Payton, Antony, Pendleton, Neil and McBeth, John (2012) The non-synonymous SNP, R1150W, in SCN9A is not associated with chronic widespread pain susceptibility. Molecular Pain, 8, [72]. (doi:10.1186/1744-8069-8-72).

Record type: Article

Abstract

Background: Mutations in SCN9A, encoding the alpha subunit of the voltage-gated sodium channel (Nav1.7), have caused severe pain disorders and congenital insensitivity to pain. The aim of this study was to validate the previously reported association between a common non-synonymous polymorphism (R1150W, rs6746030) in SCN9A and chronic widespread pain (CWP), in independent population-based cohorts.Findings: Genotype data for rs6746030 was available in four population-based cohorts (EPIFUND, the European Male Ageing Study (EMAS), the Framingham study and the Dyne Steel DNA Bank of Ageing and Cognition). Pain was assessed using body manikins and CWP was scored using American College of Rheumatology (ACR) criteria in all cohorts, except the Framingham study which assessed widespread pain (WP) using ACR criteria on a joint pain homunculus. Controls were subjects who reported no pain. Logistic regression (additive genetic model) was used to test for association between rs6746030 and CWP compared to controls, adjusting for study centre in EMAS. Generalised estimating equation regression was used to test for association between rs6746030 and WP, whilst accounting for relatedness between subjects in the Framingham study.Genotype data for rs6746030 was available for 1071 CWP cases and 3212 controls. There was no significant association between CWP and rs6476030 in individual cohorts or when combined in a fixed-effects meta-analysis (Odds Ratio = 0.96 (95% confidence interval 0.82, 1.11) p = 0.567).Conclusions: In contrast to a previous study, no association between a non-synonymous polymorphism in SCN9A and CWP was observed in multiple population-based cohorts.

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More information

Published date: 24 September 2012
Keywords: Chronic widespread pain, Population-based cohorts, Single nucleotide polymorphism, Voltage-gated sodium channel

Identifiers

Local EPrints ID: 492964
URI: http://eprints.soton.ac.uk/id/eprint/492964
ISSN: 1744-8069
PURE UUID: a5d52ed0-70a9-455e-931f-8995b02227f1
ORCID for John McBeth: ORCID iD orcid.org/0000-0001-7047-2183

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Date deposited: 21 Aug 2024 17:03
Last modified: 22 Aug 2024 02:11

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Contributors

Author: Kate L. Holliday
Author: Wendy Thomson
Author: Tuhina Neogi
Author: David T. Felson
Author: Ke Wang
Author: Frederick C. Wu
Author: Ilpo T. Huhtaniemi
Author: Gyorgy Bartfai
Author: Felipe Casanueva
Author: Gianni Forti
Author: Krzysztof Kula
Author: Margus Punab
Author: Dirk Vanderschueren
Author: Gary J. Macfarlane
Author: Michael A. Horan
Author: William Ollier
Author: Antony Payton
Author: Neil Pendleton
Author: John McBeth ORCID iD

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