title: The non-synonymous SNP, R1150W, in SCN9A is not associated with chronic widespread pain susceptibility.
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.
  
  
  RESULTS
  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.
authors.affiliation: Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. Kate.holliday@manchester.ac.uk
authors.forename: Kate L
authors.initials: KL
authors.lastname: Holliday
authors.forename: Wendy
authors.initials: W
authors.lastname: Thomson
authors.forename: Tuhina
authors.initials: T
authors.lastname: Neogi
authors.forename: David T
authors.initials: DT
authors.lastname: Felson
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Frederick C
authors.initials: FC
authors.lastname: Wu
authors.forename: Ilpo T
authors.initials: IT
authors.lastname: Huhtaniemi
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Bartfai
authors.forename: Felipe
authors.initials: F
authors.lastname: Casanueva
authors.forename: Gianni
authors.initials: G
authors.lastname: Forti
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kula
authors.forename: Margus
authors.initials: M
authors.lastname: Punab
authors.forename: Dirk
authors.initials: D
authors.lastname: Vanderschueren
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Macfarlane
authors.forename: Michael A
authors.initials: MA
authors.lastname: Horan
authors.forename: William
authors.initials: W
authors.lastname: Ollier
authors.forename: Antony
authors.initials: A
authors.lastname: Payton
authors.forename: Neil
authors.initials: N
authors.lastname: Pendleton
authors.forename: John
authors.initials: J
authors.lastname: McBeth
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics*; D059350:Chronic Pain / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human