CpG Methylation and Reduced Expression of O6-Methylguanine DNA Methyltransferase Is Associated With Helicobacter pylori Infection
DNA Repair; Eradication; MGMT; O6-Methylguanine DNA Methyltransferase
Background & Aims: The gastric epithelium genome undergoes extensive epigenetic alterations during Helicobacter pylori-induced gastritis. Expression of the gene encoding the DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) might be reduced via hypermethylation of its promoter in patients with H pylori gastritis. We characterized expression of MGMT and its epigenetic regulation via CpG methylation in gastric tissue from patients with H pylori gastritis and investigated the effects of H pylori infection eradication on MGMT expression. Methods: Gastric biopsy samples were collected from patients with H pylori gastritis before and after eradication and from H pylori-negative control subjects. AGS cells were cocultured with H pylori to study the effects of H pylori infection on MGMT RNA, protein expression, and CpG methylation. Results: CpG methylation of MGMT was more frequent in the gastric mucosa of patients with H pylori gastritis (69.7%) than in those without (28.6%, P = .022). MGMT methylation was significantly reduced after H pylori eradication (from 70% to 48% of cases, P = .039), and mean levels of CpG methylation decreased from 12.6% to 5.7% (P = .025), increasing MGMT expression. MGMT methylation was significantly associated with CagA-positive H pylori (P = .035). H pylori reduced MGMT protein and RNA levels and induced MGMT CpG methylation in gastric AGS cells. Conclusions: H pylori gastritis, particularly in patients infected with H pylori CagA-positive strains, is associated with hypermethylation of MGMT and reduced levels of MGMT in the gastric epithelium. MGMT promoter methylation is partially reversible after eradication of H pylori infection. These data indicate that DNA repair is disrupted during H pylori gastritis, increasing mutagenesis in H pylori-infected gastric mucosa. © 2010 AGA Institute.
Sepulveda, A., Yao, Y., Yan, W., Park, D., Kim, J., Gooding, W., Abudayyeh, S., & Graham, D. (2010). CpG Methylation and Reduced Expression of O6-Methylguanine DNA Methyltransferase Is Associated With Helicobacter pylori Infection. Gastroenterology, 138 (5). http://dx.doi.org/10.1053/j.gastro.2009.12.042