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

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

*Corresponding author for this work

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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.

Original languageEnglish
Article number72
Number of pages5
JournalMolecular Pain
Volume8
Early online date1 Jan 2012
DOIs
Publication statusPublished - 24 Sep 2012

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Keywords

  • Chronic widespread pain
  • Population-based cohorts
  • Single nucleotide polymorphism
  • Voltage-gated sodium channel

ASJC Scopus subject areas

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Anesthesiology and Pain Medicine

Cite this

Holliday, K. L., Thomson, W., Neogi, T., Felson, D. T., Wang, K., Wu, F. C., ... McBeth, J. (2012). The non-synonymous SNP, R1150W, in SCN9A is not associated with chronic widespread pain susceptibility. Molecular Pain, 8, [72]. https://doi.org/10.1186/1744-8069-8-72