Genetic polymorphism of pri-microRNA 325, targeting SLC6A4 3′-UTR, is closely associated with the risk of functional dyspepsia in Japan

Tomiyasu Arisawa, Tomomitsu Tahara, Tomoki Fukuyama, Ranji Hayashi, Kazuhiro Matsunaga, Nobuhiko Hayashi, Masakatsu Nakamura, Nobuyuki Toshikuni, Hisakazu Shiroeda, Tomoyuki Shibata

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Abstract

Background: The role of genetics in the susceptibility to functional dyspepsia (FD) remains unclear. We attempted to clarify the association between FD and polymorphisms in SLC6A4. In addition, rs5981521 (C>T) in the pri-microRNA 325 (pri-miR-325) coding region was also investigated. Methods: The study was performed in 395 subjects (172 with no upper abdominal symptoms and 223 with FD, including medication-resistant FD). We employed a polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method to detect gene polymorphisms. Results: Neither SLC6A4 -185 A>C nor*463 G>T was associated with susceptibility to FD. The number of rs5981521 T alleles was significantly correlated with an increased risk for FD (odds ratio [OR] 1.45, 95 % confidence interval [CI] 1.05-1.98; p = 0.022) and the TT homozygote was more closely associated with the risk for FD (OR 3.01, 95 % CI 1.41-6.42; p = 0.0043). The TT homozygote also had significantly increased risks for both the epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) subtypes of FD (OR 3.04, 95 % CI 1.25-7.42; p = 0.014 and OR 3.05, 95 % CI 1.14-8.13; p = 0.026, respectively). In addition, Helicobacter pylori-negative TT homozygotes had a greater risk for FD (OR 8.37, 95 % CI 1.78-39.5; p = 0.0072). In subjects with the SLC6A4 5′-untranslated region (UTR) wild homozygote, the number of rs5981521 T alleles was significantly correlated to an increased risk for FD (OR 1.45, 95 % CI 1.03-2.04, p = 0.033). Of note, in subjects who were SLC6A4 3′-UTR mutant carriers, the number of rs5981521 T alleles was also significantly correlated with an increased risk for FD (OR 2.07, 95 % CI 1.08-3.98; p = 0.029). Conclusions: Our results suggest that the genetic polymorphism pri-miR-325 is associated with FD and interacts with SLC6A4 polymorphisms in increasing susceptibility to FD in Japanese.

Original languageEnglish
Pages (from-to)1091-1098
Number of pages8
JournalJournal of Gastroenterology
Volume47
Issue number10
DOIs
Publication statusPublished - 01-10-2012

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Dyspepsia
5' Untranslated Regions
3' Untranslated Regions
Genetic Polymorphisms
MicroRNAs
Japan
Odds Ratio
Confidence Intervals
Homozygote
Alleles
Genetic Predisposition to Disease
Helicobacter pylori

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Arisawa, Tomiyasu ; Tahara, Tomomitsu ; Fukuyama, Tomoki ; Hayashi, Ranji ; Matsunaga, Kazuhiro ; Hayashi, Nobuhiko ; Nakamura, Masakatsu ; Toshikuni, Nobuyuki ; Shiroeda, Hisakazu ; Shibata, Tomoyuki. / Genetic polymorphism of pri-microRNA 325, targeting SLC6A4 3′-UTR, is closely associated with the risk of functional dyspepsia in Japan. In: Journal of Gastroenterology. 2012 ; Vol. 47, No. 10. pp. 1091-1098.
@article{c81c37ad5c66441a99c8b818667c3911,
title = "Genetic polymorphism of pri-microRNA 325, targeting SLC6A4 3′-UTR, is closely associated with the risk of functional dyspepsia in Japan",
abstract = "Background: The role of genetics in the susceptibility to functional dyspepsia (FD) remains unclear. We attempted to clarify the association between FD and polymorphisms in SLC6A4. In addition, rs5981521 (C>T) in the pri-microRNA 325 (pri-miR-325) coding region was also investigated. Methods: The study was performed in 395 subjects (172 with no upper abdominal symptoms and 223 with FD, including medication-resistant FD). We employed a polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method to detect gene polymorphisms. Results: Neither SLC6A4 -185 A>C nor*463 G>T was associated with susceptibility to FD. The number of rs5981521 T alleles was significantly correlated with an increased risk for FD (odds ratio [OR] 1.45, 95 {\%} confidence interval [CI] 1.05-1.98; p = 0.022) and the TT homozygote was more closely associated with the risk for FD (OR 3.01, 95 {\%} CI 1.41-6.42; p = 0.0043). The TT homozygote also had significantly increased risks for both the epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) subtypes of FD (OR 3.04, 95 {\%} CI 1.25-7.42; p = 0.014 and OR 3.05, 95 {\%} CI 1.14-8.13; p = 0.026, respectively). In addition, Helicobacter pylori-negative TT homozygotes had a greater risk for FD (OR 8.37, 95 {\%} CI 1.78-39.5; p = 0.0072). In subjects with the SLC6A4 5′-untranslated region (UTR) wild homozygote, the number of rs5981521 T alleles was significantly correlated to an increased risk for FD (OR 1.45, 95 {\%} CI 1.03-2.04, p = 0.033). Of note, in subjects who were SLC6A4 3′-UTR mutant carriers, the number of rs5981521 T alleles was also significantly correlated with an increased risk for FD (OR 2.07, 95 {\%} CI 1.08-3.98; p = 0.029). Conclusions: Our results suggest that the genetic polymorphism pri-miR-325 is associated with FD and interacts with SLC6A4 polymorphisms in increasing susceptibility to FD in Japanese.",
author = "Tomiyasu Arisawa and Tomomitsu Tahara and Tomoki Fukuyama and Ranji Hayashi and Kazuhiro Matsunaga and Nobuhiko Hayashi and Masakatsu Nakamura and Nobuyuki Toshikuni and Hisakazu Shiroeda and Tomoyuki Shibata",
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language = "English",
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pages = "1091--1098",
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Arisawa, T, Tahara, T, Fukuyama, T, Hayashi, R, Matsunaga, K, Hayashi, N, Nakamura, M, Toshikuni, N, Shiroeda, H & Shibata, T 2012, 'Genetic polymorphism of pri-microRNA 325, targeting SLC6A4 3′-UTR, is closely associated with the risk of functional dyspepsia in Japan', Journal of Gastroenterology, vol. 47, no. 10, pp. 1091-1098. https://doi.org/10.1007/s00535-012-0576-1

Genetic polymorphism of pri-microRNA 325, targeting SLC6A4 3′-UTR, is closely associated with the risk of functional dyspepsia in Japan. / Arisawa, Tomiyasu; Tahara, Tomomitsu; Fukuyama, Tomoki; Hayashi, Ranji; Matsunaga, Kazuhiro; Hayashi, Nobuhiko; Nakamura, Masakatsu; Toshikuni, Nobuyuki; Shiroeda, Hisakazu; Shibata, Tomoyuki.

In: Journal of Gastroenterology, Vol. 47, No. 10, 01.10.2012, p. 1091-1098.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic polymorphism of pri-microRNA 325, targeting SLC6A4 3′-UTR, is closely associated with the risk of functional dyspepsia in Japan

AU - Arisawa, Tomiyasu

AU - Tahara, Tomomitsu

AU - Fukuyama, Tomoki

AU - Hayashi, Ranji

AU - Matsunaga, Kazuhiro

AU - Hayashi, Nobuhiko

AU - Nakamura, Masakatsu

AU - Toshikuni, Nobuyuki

AU - Shiroeda, Hisakazu

AU - Shibata, Tomoyuki

PY - 2012/10/1

Y1 - 2012/10/1

N2 - Background: The role of genetics in the susceptibility to functional dyspepsia (FD) remains unclear. We attempted to clarify the association between FD and polymorphisms in SLC6A4. In addition, rs5981521 (C>T) in the pri-microRNA 325 (pri-miR-325) coding region was also investigated. Methods: The study was performed in 395 subjects (172 with no upper abdominal symptoms and 223 with FD, including medication-resistant FD). We employed a polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method to detect gene polymorphisms. Results: Neither SLC6A4 -185 A>C nor*463 G>T was associated with susceptibility to FD. The number of rs5981521 T alleles was significantly correlated with an increased risk for FD (odds ratio [OR] 1.45, 95 % confidence interval [CI] 1.05-1.98; p = 0.022) and the TT homozygote was more closely associated with the risk for FD (OR 3.01, 95 % CI 1.41-6.42; p = 0.0043). The TT homozygote also had significantly increased risks for both the epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) subtypes of FD (OR 3.04, 95 % CI 1.25-7.42; p = 0.014 and OR 3.05, 95 % CI 1.14-8.13; p = 0.026, respectively). In addition, Helicobacter pylori-negative TT homozygotes had a greater risk for FD (OR 8.37, 95 % CI 1.78-39.5; p = 0.0072). In subjects with the SLC6A4 5′-untranslated region (UTR) wild homozygote, the number of rs5981521 T alleles was significantly correlated to an increased risk for FD (OR 1.45, 95 % CI 1.03-2.04, p = 0.033). Of note, in subjects who were SLC6A4 3′-UTR mutant carriers, the number of rs5981521 T alleles was also significantly correlated with an increased risk for FD (OR 2.07, 95 % CI 1.08-3.98; p = 0.029). Conclusions: Our results suggest that the genetic polymorphism pri-miR-325 is associated with FD and interacts with SLC6A4 polymorphisms in increasing susceptibility to FD in Japanese.

AB - Background: The role of genetics in the susceptibility to functional dyspepsia (FD) remains unclear. We attempted to clarify the association between FD and polymorphisms in SLC6A4. In addition, rs5981521 (C>T) in the pri-microRNA 325 (pri-miR-325) coding region was also investigated. Methods: The study was performed in 395 subjects (172 with no upper abdominal symptoms and 223 with FD, including medication-resistant FD). We employed a polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method to detect gene polymorphisms. Results: Neither SLC6A4 -185 A>C nor*463 G>T was associated with susceptibility to FD. The number of rs5981521 T alleles was significantly correlated with an increased risk for FD (odds ratio [OR] 1.45, 95 % confidence interval [CI] 1.05-1.98; p = 0.022) and the TT homozygote was more closely associated with the risk for FD (OR 3.01, 95 % CI 1.41-6.42; p = 0.0043). The TT homozygote also had significantly increased risks for both the epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) subtypes of FD (OR 3.04, 95 % CI 1.25-7.42; p = 0.014 and OR 3.05, 95 % CI 1.14-8.13; p = 0.026, respectively). In addition, Helicobacter pylori-negative TT homozygotes had a greater risk for FD (OR 8.37, 95 % CI 1.78-39.5; p = 0.0072). In subjects with the SLC6A4 5′-untranslated region (UTR) wild homozygote, the number of rs5981521 T alleles was significantly correlated to an increased risk for FD (OR 1.45, 95 % CI 1.03-2.04, p = 0.033). Of note, in subjects who were SLC6A4 3′-UTR mutant carriers, the number of rs5981521 T alleles was also significantly correlated with an increased risk for FD (OR 2.07, 95 % CI 1.08-3.98; p = 0.029). Conclusions: Our results suggest that the genetic polymorphism pri-miR-325 is associated with FD and interacts with SLC6A4 polymorphisms in increasing susceptibility to FD in Japanese.

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