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Autoimmune gastritis induces aberrant DNA methylation reflecting its carcinogenic potential
Ist Teil von
Journal of gastroenterology, 2022-03, Vol.57 (3), p.144-155
Ort / Verlag
Singapore: Springer Singapore
Erscheinungsjahr
2022
Quelle
MEDLINE
Beschreibungen/Notizen
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.