title: Change in DNA methylation patterns of SLC6A4 gene in the gastric mucosa in functional dyspepsia.
abstract: BACKGROUND
  The neurochemical serotonin (5-HT) is an important signaling molecule in the gastrointestinal motor and sensory functions. A key regulator of 5-HT levels is the transmembrane serotonin transporter (5-HTT; SLC6A4) that governs the reuptake of 5-HT. Recent studies have indicated 5-HTT expression may be regulated by epigenetic mechanisms. We investigated DNA methylation status of SLC6A4 gene in the gastric mucosa from functional dyspepsia (FD) because of their potential role in dyspeptic symptoms.
  
  
  METHODS
  Endoscopic gastric biopsies were obtained from 78 subjects with no upper abdominal symptoms and 79 patients with FD. Bisulfite Pyrosequencing was carried out to determine the methylation status of promoter CpG islands (PCGIs), promoter non-CpG islands (PNCGIs) and gene body non-CpG islands (NPNCGIs) in the SLC6A4 gene. Gene expression was examined by real-time PCR.
  
  
  RESULTS
  In overall, methylation level of PCGIs was significantly lower in FD compared to control subjects (p = 0.04). On the other hand, methylation level of NPNCGIs was significantly higher in FD compared to control subjects (p = 0.03). Lower methylation level in PNCGIs was highlighted in the patients with PDS (p = 0.01), while higher methylation level in NPNCGIs was more prominent in the patients with EPS (p = 0.017). Methylation levels of PCGIs and PNCGIs were inversely correlated, while methylation levels of NPNCGIs was positively correlated with SLC6A4 mRNA levels in FD patients.
  
  
  CONCLUSIONS
  Our data suggest that change in DNA methylation pattern of SLC6A4 in the gastric mucosa may have a role for developing FD. A role of epigenetics for developing FD needs to be further evaluated.
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Okubo
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Sumi
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Ishizuka
authors.affiliation: Department of Gastroenterology, Kanazawa Medical University, Uchinadamachi, Ishikawa, Japan.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nagasaka
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ohmiya
authors.affiliation: Department of Gastroenterology, Kanazawa Medical University, Uchinadamachi, Ishikawa, Japan.
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Arisawa
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirata
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D004415:Dyspepsia / Q000235:genetics* / Q000382:microbiology / Q000503:physiopathology; D044127:Epigenesis, Genetic; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins