Change in DNA methylation patterns of SLC6A4 gene in the gastric mucosa in functional dyspepsia

Tomomitsu Tahara, Tomoyuki Shibata, Masaaki Okubo, Kazuya Sumi, Takamitsu Ishizuka, Masakatsu Nakamura, Mitsuo Nagasaka, Yoshihito Nakagawa, Naoki Omiya, Tomiyasu Arisawa, Ichiro Hirata

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Article numbere105565
JournalPloS one
Volume9
Issue number8
DOIs
Publication statusPublished - 22-08-2014

Fingerprint

indigestion
Methylation
gastric mucosa
Dyspepsia
DNA methylation
DNA Methylation
Gastric Mucosa
methylation
Genes
serotonin
promoter regions
Islands
CpG Islands
Serotonin
genes
Epigenomics
epigenetics
signs and symptoms (animals and humans)
bisulfites
Serotonin Plasma Membrane Transport Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Tahara, T., Shibata, T., Okubo, M., Sumi, K., Ishizuka, T., Nakamura, M., ... Hirata, I. (2014). Change in DNA methylation patterns of SLC6A4 gene in the gastric mucosa in functional dyspepsia. PloS one, 9(8), [e105565]. https://doi.org/10.1371/journal.pone.0105565
Tahara, Tomomitsu ; Shibata, Tomoyuki ; Okubo, Masaaki ; Sumi, Kazuya ; Ishizuka, Takamitsu ; Nakamura, Masakatsu ; Nagasaka, Mitsuo ; Nakagawa, Yoshihito ; Omiya, Naoki ; Arisawa, Tomiyasu ; Hirata, Ichiro. / Change in DNA methylation patterns of SLC6A4 gene in the gastric mucosa in functional dyspepsia. In: PloS one. 2014 ; Vol. 9, No. 8.
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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.",
author = "Tomomitsu Tahara and Tomoyuki Shibata and Masaaki Okubo and Kazuya Sumi and Takamitsu Ishizuka and Masakatsu Nakamura and Mitsuo Nagasaka and Yoshihito Nakagawa and Naoki Omiya and Tomiyasu Arisawa and Ichiro Hirata",
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Tahara, T, Shibata, T, Okubo, M, Sumi, K, Ishizuka, T, Nakamura, M, Nagasaka, M, Nakagawa, Y, Omiya, N, Arisawa, T & Hirata, I 2014, 'Change in DNA methylation patterns of SLC6A4 gene in the gastric mucosa in functional dyspepsia', PloS one, vol. 9, no. 8, e105565. https://doi.org/10.1371/journal.pone.0105565

Change in DNA methylation patterns of SLC6A4 gene in the gastric mucosa in functional dyspepsia. / Tahara, Tomomitsu; Shibata, Tomoyuki; Okubo, Masaaki; Sumi, Kazuya; Ishizuka, Takamitsu; Nakamura, Masakatsu; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Omiya, Naoki; Arisawa, Tomiyasu; Hirata, Ichiro.

In: PloS one, Vol. 9, No. 8, e105565, 22.08.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Change in DNA methylation patterns of SLC6A4 gene in the gastric mucosa in functional dyspepsia

AU - Tahara, Tomomitsu

AU - Shibata, Tomoyuki

AU - Okubo, Masaaki

AU - Sumi, Kazuya

AU - Ishizuka, Takamitsu

AU - Nakamura, Masakatsu

AU - Nagasaka, Mitsuo

AU - Nakagawa, Yoshihito

AU - Omiya, Naoki

AU - Arisawa, Tomiyasu

AU - Hirata, Ichiro

PY - 2014/8/22

Y1 - 2014/8/22

N2 - 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.

AB - 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.

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