title: Genetic polymorphisms of SCN10A are associated with functional dyspepsia in Japanese subjects.
abstract: BACKGROUND
  Visceral sensory impulses are transmitted via C-fibers from the gastrointestinal tract to the central nervous system. The tetrodotoxinresistant (TTX-r) sodium channel, Na(V) 1.8/SNS (sensory-neuron specific), encoded by SCN10A, has been identified on C-fibers. We attempted to clarify the association between functional dyspepsia (FD) and SCN10A non-synonymous polymorphisms (2884 A>G, 3218 C>T and 3275 T>C).
  
  
  METHODS
  The study was performed in 642 subjects (345 with no symptoms and 297 with FD). We employed a multiplex polymerase chain reaction single-strand confirmation polymorphism (PCR-SSCP) method to detect the gene polymorphisms.
  
  
  RESULTS
  The 3218 CC homozygotes had a reduced risk for the development of FD [odds ratio (OR) 0.589; 95 % confidence interval (CI) 0.402-0.864; p = 0.0067]. In addition, both 2884 A>G and 3275 T>C, which were in linkage disequilibrium, were also associated with the development of FD (p = 0.039 and 0.028, respectively). Each 2884 G carrier, 3218 CC homozygote, and 3275 C carrier had a reduced risk for the development of both epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). The subjects with the 2884 G allele, 3275 C allele, and no 3218 T allele had a reduced risk for FD (OR 0.618; 95 % CI 0.448-0.853; p = 0.0034). This haplotype was associated with a reduced risk for both EPS and PDS (p = 0.0011 and 0.0056, respectively). In addition, there was a significant association between FD and this haplotype in Helicobacter pylori-negative subjects (OR 0.463; 95 % CI 0279-0.9768; p = 0.0029).
  
  
  CONCLUSIONS
  We conclude that genetic polymorphisms of SCN10A are closely associated with FD (both EPS and PDS), especially in H. pylori-negative subjects, in Japanese.
authors.affiliation: Department of Gastroenterology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa, 920-0293, Japan. tarisawa@kanazawa-med.ac.jp
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Arisawa
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Shiroeda
authors.forename: Takahiro
authors.initials: T
authors.lastname: Minato
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsue
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.forename: Tomoki
authors.initials: T
authors.lastname: Fukuyama
authors.forename: Toshimi
authors.initials: T
authors.lastname: Otsuka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukumura
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
mesh_terms: D015746:Abdominal Pain / Q000150:complications / Q000235:genetics; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016001:Confidence Intervals; D004415:Dyspepsia / Q000150:complications / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006720:Homozygote; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000235:genetics*; D036421:Nerve Fibers, Unmyelinated; D059225:Nociception; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period; D013577:Syndrome; D017833:Visceral Afferents
chemical_list: D062559:NAV1.8 Voltage-Gated Sodium Channel; C568317:SCN10A protein, human