Genetic polymorphisms of SCN10A are associated with functional dyspepsia in Japanese subjects

• Published in: Journal of gastroenterology 2013, Vol.48 (1), p.73-80
• Main Authors: Arisawa, Tomiyasu, Tahara, Tomomitsu, Shiroeda, Hisakazu, Minato, Takahiro, Matsue, Yasuhiro, Saito, Takashi, Fukuyama, Tomoki, Otsuka, Toshimi, Fukumura, Atsushi, Nakamura, Masakatsu, Shibata, Tomoyuki
• Format: Article
• Language: English
• Subjects: Abdominal Pain - complications; Abdominal Pain - genetics; Abdominal Surgery; Adult; Aged; Alleles; Asian Continental Ancestry Group - genetics; Central nervous system; Colorectal Surgery; Confidence Intervals; Dyspepsia; Dyspepsia - complications; Dyspepsia - genetics; Female; Gastroenterology; Genetic aspects; Genetic polymorphisms; Genetic research; Haplotypes; Helicobacter; Helicobacter Infections - complications; Helicobacter pylori; Hepatology; Homozygote; Humans; Japan; Male; Medicine; Medicine & Public Health; Middle Aged; NAV1.8 Voltage-Gated Sodium Channel - genetics; Nerve Fibers, Unmyelinated; Nociception; Odds Ratio; Original Article—Alimentary Tract; Polymorphism, Single Nucleotide; Postprandial Period; Surgical Oncology; Syndrome; Visceral Afferents
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-012-0602-3

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). Conclusion We conclude that genetic polymorphisms of SCN10A are closely associated with FD (both EPS and PDS), especially in H. pylori -negative subjects, in Japanese.