DNMT1 Gene Expression in Patients with Helicobacter pylori Infection
Manouchehr Ahmadi Hedayati1,2, Amjad Ahmadi3,4, Zahed Khatooni5
1Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Abstract:
DNMT1, as a critical enzyme affecting epigenetics through methylation of DNA cytosine-rich sequences, regulates gene expression. Exterior factors including long-term infections, in this study Helicobacter pylori infection, could change host cells' epigenetics by affecting DNMT1 gene expression. This study investigated the statistical correlation between H. pylori virulence genes and DNMT1 gene expression in gastric antral epithelial cells of gastric adenocarcinoma and gastritis patients. In a case-control study, 50 and 53 gastritis and gastric adenocarcinoma antral biopsies, including 23 and 21 patients with H. pylori infection, respectively, were collected from hospitals in the west of Iran. Having extracted total RNA from gastric biopsy samples, cDNA was synthesized and virulence genes of H. pylori were detected by using the PCR method. Relative real-time RT PCR was used to detect ΔΔCt fold changes of the DNMT1 gene expression in divided groups of patients based on H. pylori infection and clinical manifestations. The results showed that along with increasing patients' age, the DNMT1 gene expression will increase in gastric antral epithelial cells of gastric cancer patients (P ≤ 0.05). On the other hand, the biopsy samples with infection of H. pylori cagA, cagY, and cagE genotypes revealed a direct correlation along with increased DNMT1 gene expression. This study revealed the correlations of H. pylori cag pathogenicity island genes with increased DNMT1 gene expression.
Insights
Helicobacter pylori infection, particularly strains with cagA, cagY, and cagE virulence genes, is linked to increased DNMT1 gene expression in gastric tissues. This epigenetic change may play a role in gastric diseases.
Area of Science:
- Epigenetics
- Molecular biology
- Gastroenterology
Background:
- DNA methyltransferase 1 (DNMT1) regulates gene expression through DNA methylation.
- Epigenetic modifications can be influenced by external factors like Helicobacter pylori (H. pylori) infection.
- H. pylori infection is a known risk factor for gastric diseases.
Purpose of the Study:
- To investigate the correlation between H. pylori virulence genes and DNMT1 gene expression.
- To analyze DNMT1 expression in gastric epithelial cells of gastritis and gastric adenocarcinoma patients.
- To explore the relationship between H. pylori infection, specific virulence factors, and epigenetic changes.
Main Methods:
- Case-control study involving gastric biopsies from gastritis and gastric adenocarcinoma patients.
- RNA extraction, cDNA synthesis, and Polymerase Chain Reaction (PCR) for H. pylori virulence gene detection.
- Relative real-time RT PCR to quantify DNMT1 gene expression (ΔΔCt fold changes).
Main Results:
- DNMT1 gene expression increased with patient age in gastric cancer samples (P ≤ 0.05).
- H. pylori infection, specifically cagA, cagY, and cagE genotypes, showed a direct correlation with elevated DNMT1 expression.
- A significant association was found between H. pylori cag pathogenicity island genes and increased DNMT1 expression.
Conclusions:
- H. pylori cag pathogenicity island genes are correlated with increased DNMT1 gene expression in gastric epithelial cells.
- These findings suggest a potential epigenetic mechanism linking H. pylori infection to gastric pathogenesis.
- Further research is warranted to elucidate the precise role of DNMT1 in H. pylori-associated gastric diseases.
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