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

Tomiyasu Arisawa, Tomomitsu Tahara, Hisakazu Shiroeda, Takahiro Minato, Yasuhiro Matsue, Takashi Saito, Tomoki Fukuyama, Toshimi Otsuka, Atsushi Fukumura, Masakatsu Nakamura, Tomoyuki Shibata

Research output: Contribution to journalArticle

19 Citations (Scopus)

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). 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.

Original languageEnglish
Pages (from-to)73-80
Number of pages8
JournalJournal of Gastroenterology
Volume48
Issue number1
DOIs
Publication statusPublished - 01-01-2013

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Dyspepsia
Genetic Polymorphisms
Unmyelinated Nerve Fibers
Alleles
Odds Ratio
Homozygote
Confidence Intervals
Helicobacter pylori
Pain
Haplotypes
Sodium Channels
Multiplex Polymerase Chain Reaction
Linkage Disequilibrium
Sensory Receptor Cells
Gastrointestinal Tract
Central Nervous System
Genes

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Arisawa, Tomiyasu ; Tahara, Tomomitsu ; Shiroeda, Hisakazu ; Minato, Takahiro ; Matsue, Yasuhiro ; Saito, Takashi ; Fukuyama, Tomoki ; Otsuka, Toshimi ; Fukumura, Atsushi ; Nakamura, Masakatsu ; Shibata, Tomoyuki. / Genetic polymorphisms of SCN10A are associated with functional dyspepsia in Japanese subjects. In: Journal of Gastroenterology. 2013 ; Vol. 48, No. 1. pp. 73-80.
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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). 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.",
author = "Tomiyasu Arisawa and Tomomitsu Tahara and Hisakazu Shiroeda and Takahiro Minato and Yasuhiro Matsue and Takashi Saito and Tomoki Fukuyama and Toshimi Otsuka and Atsushi Fukumura and Masakatsu Nakamura and Tomoyuki Shibata",
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Arisawa, T, Tahara, T, Shiroeda, H, Minato, T, Matsue, Y, Saito, T, Fukuyama, T, Otsuka, T, Fukumura, A, Nakamura, M & Shibata, T 2013, 'Genetic polymorphisms of SCN10A are associated with functional dyspepsia in Japanese subjects', Journal of Gastroenterology, vol. 48, no. 1, pp. 73-80. https://doi.org/10.1007/s00535-012-0602-3

Genetic polymorphisms of SCN10A are associated with functional dyspepsia in Japanese subjects. / Arisawa, Tomiyasu; Tahara, Tomomitsu; Shiroeda, Hisakazu; Minato, Takahiro; Matsue, Yasuhiro; Saito, Takashi; Fukuyama, Tomoki; Otsuka, Toshimi; Fukumura, Atsushi; Nakamura, Masakatsu; Shibata, Tomoyuki.

In: Journal of Gastroenterology, Vol. 48, No. 1, 01.01.2013, p. 73-80.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic polymorphisms of SCN10A are associated with functional dyspepsia in Japanese subjects

AU - Arisawa, Tomiyasu

AU - Tahara, Tomomitsu

AU - Shiroeda, Hisakazu

AU - Minato, Takahiro

AU - Matsue, Yasuhiro

AU - Saito, Takashi

AU - Fukuyama, Tomoki

AU - Otsuka, Toshimi

AU - Fukumura, Atsushi

AU - Nakamura, Masakatsu

AU - Shibata, Tomoyuki

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

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