Autoimmune gastritis induces aberrant DNA methylation reflecting its carcinogenic potential

Chihiro Takeuchi, Junichi Sato, Satoshi Yamashita, Akiko Sasaki, Takemi Akahane, Rika Aoki, Mitsue Yamamichi, Yu Yu Liu, Masayoshi Ito, Takahisa Furuta, Shigemi Nakajima, Yoshiki Sakaguchi, Yu Takahashi, Yosuke Tsuji, Keiko Niimi, Shuta Tomida, Mitsuhiro Fujishiro, Nobutake Yamamichi, Toshikazu Ushijima

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Autoimmune gastritis (AIG) is a chronic inflammatory condition in gastric mucosa and is associated with increased cancer risk, though not as high as that by Helicobacter pylori (H. pylori)-associated gastritis (HPG). Although aberrant DNA methylation is induced by HPG and the level correlates with the risk of gastric cancer, DNA methylation induction by AIG is unknown. Methods: Gastric mucosa samples from the corpus were collected from 12 people with AIG without H. pylori infection, 10 people with HPG, and eight healthy volunteers. Genome-wide DNA methylation analysis was conducted using Infinium Methylation EPIC array. Gene expression was analyzed by quantitative RT-PCR. Results: The AIG samples had extensive aberrant DNA methylation but presented unique methylation profiles against the HPG samples after correction of leucocyte fractions. Comparison between the AIG and HPG samples showed that AIG induced methylation, but less than HPG, in overall CpG sites and also in promoter CpG islands. Promoter CpG islands of tumor-suppressor genes in the pathway of cell cycle, cell adhesion, p53, and WNT were highly methylated in the AIG samples, but more so in the HPG samples. The expression levels of IL1B and IL8, secreted by macrophage, were significantly lower in the AIG samples than in the HPG samples, suggesting that a difference in inflammatory response affected the degree and patterns of aberrant DNA methylation. Conclusions: AIG induced aberrant DNA methylation in gastric mucosa. However, the degree of DNA methylation was less than that by HPG, which reflected carcinogenic risk.

Original languageEnglish
Pages (from-to)144-155
Number of pages12
JournalJournal of Gastroenterology
Volume57
Issue number3
DOIs
Publication statusPublished - Mar 2022

Keywords

  • Autoimmune gastritis
  • DNA methylation
  • Epigenetics
  • Helicobacter pylori
  • Molecular epidemiology

ASJC Scopus subject areas

  • Gastroenterology

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