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Autoimmune gastritis induces aberrant DNA methylation reflecting its carcinogenic potential

  • Original Article—Alimentary Tract
  • Published:
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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.

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Data availability

The microarray data of genome-wide DNA methylation analysis were deposited at Gene Expression Omnibus (GSE178925).

Abbreviations

AIG:

Autoimmune gastritis

H. pylori :

Helicobacter pylori

HPG:

Helicobacter pylori-associated gastritis

PCA:

Anti-parietal cell antibodies

TSSs:

Transcription start sites

CGIs:

CpG islands

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Acknowledgements

This work was supported by a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science (21H03178).

Author information

Author notes

  1. Chihiro Takeuchi and Junichi Sato have contributed equally to this work.

Authors and Affiliations

  1. Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan

    Chihiro Takeuchi, Satoshi Yamashita, Yu-Yu Liu & Toshikazu Ushijima

  2. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Junichi Sato, Mitsue Yamamichi, Yoshiki Sakaguchi, Yu Takahashi, Yosuke Tsuji & Mitsuhiro Fujishiro

  3. Department of Gastroenterology, Medicine Center, Shonan Kamakura General Hospital, Kanagawa, Japan

    Akiko Sasaki

  4. Department of Gastroenterology, Nara Medical University, Nara, Japan

    Takemi Akahane

  5. Tokushima Health Screening Center, Tokushima, Japan

    Rika Aoki

  6. Department of Gastroenterology, Yotsuya Medical Cube, Tokyo, Japan

    Masayoshi Ito

  7. Center for Clinical Research, Hamamatsu University School of Medicine, Shizuoka, Japan

    Takahisa Furuta

  8. Department of General Medicine, Consortium for Community Medicine, Japan Community Healthcare Organization Shiga Hospital, Shiga University of Medical Science, Shiga, Japan

    Shigemi Nakajima

  9. Center for Epidemiology and Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Keiko Niimi & Nobutake Yamamichi

  10. Center for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Japan

    Shuta Tomida

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  1. Chihiro Takeuchi
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Contributions

Conception and design: CT, JS, KN, NY, and TU. Development of methodology: CT, SY, and TU. Acquisition of data: CT, JS, MW, YS, YT, AS, TA, RA, MY, MI, TF, and SN. Analysis and interpretation of data: CT, SY, YL, and TU. Writing, review, and/or revision of the manuscript: CT, MF, NY, and TU.

Corresponding author

Correspondence to Toshikazu Ushijima.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions.

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Informed consent was obtained from all patients to be included in the study.

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Takeuchi, C., Sato, J., Yamashita, S. et al. Autoimmune gastritis induces aberrant DNA methylation reflecting its carcinogenic potential. J Gastroenterol 57, 144–155 (2022). https://doi.org/10.1007/s00535-021-01848-2

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  • DOI: https://doi.org/10.1007/s00535-021-01848-2

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