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

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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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, 47(10), 1091-1098. https://doi.org/10.1007/s00535-012-0576-1