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.
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: Tomoki
authors.initials: T
authors.lastname: Fukuyama
authors.forename: Ranji
authors.initials: R
authors.lastname: Hayashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsunaga
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hayashi
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Toshikuni
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Shiroeda
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004415:Dyspepsia / Q000235:genetics* / Q000382:microbiology; D005260:Female; D020022:Genetic Predisposition to Disease; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D007564:Japan; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D020506:Untranslated Regions
chemical_list: C576078:MIRN325 microRNA, human; D035683:MicroRNAs; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D020506:Untranslated Regions