Evaluation of the Pattern of EPIYA Motifs in the Helicobacter pylori cagA Gene of Patients with Gastritis and Gastric Adenocarcinoma from the Brazilian Amazon Region
The Helicobacter pylori is associated with the development of different diseases. The clinical outcome of infection may be associated with the cagA bacterial genotype. The aim of this study was to determine the EPIYA patterns of strains isolated from patients with gastritis and gastric adenocarcinoma and correlate these patterns with the histopathological features. Gastric biopsy samples were selected from 384 patients infected with H. pylori, including 194 with chronic gastritis and 190 with gastric adenocarcinoma. The presence of the cagA gene and the EPIYA motif was determined by PCR. The cagA gene was more prevalent in patients with gastric cancer and was associated with a higher degree of inflammation, neutrophil activity, and development of intestinal metaplasia. The number of EPIYA-C repeats showed a significant association with an increased risk of gastric carcinoma (OR = 3.79, 95% CI = 1.92–7.46, and ). A larger number of EPIYA-C motifs were also associated with intestinal metaplasia. In the present study, infection with H. pylori strains harboring more than one EPIYA-C motif in the cagA gene was associated with the development of intestinal metaplasia and gastric adenocarcinoma but not with neutrophil activity or degree of inflammation. 1. Introduction Helicobacter pylori is a spiral Gram-negative bacterium that infects the stomach and causes chronic gastritis. In addition, the bacterium plays an important role in the pathogenesis of gastroduodenal ulcer and gastric carcinoma [1]. The diverse clinical outcomes of H. pylori infection depend on factors such as bacterial virulence, host susceptibility, and environmental factors [2]. Protein-associated gene A (CagA) is an important virulence factor of H. pylori that is found in 70 to 80% of strains isolated in Brazilian cities and is associated with the development of peptic ulcers and gastric carcinoma [3, 4]. This protein is encoded by the cagA gene, which is located on the cag pathogenicity island (cag-PAI). After adhesion of cagA-positive H. pylori strains to the gastric epithelium, the CagA protein is injected directly into the host cell through a type IV secretion system encoded by the cag-PAI. Inside the epithelial cell, CagA is phosphorylated in its carboxy-terminal region. This region is highly variable and contains a polymorphic pattern of Glu-Pro-Ile-Tyr-Ala amino acid repeats (EPIYA motif) [5, 6]. Four types of EPIYA segments have been described (EPIYA-A, -B, -C, and -D) [7, 8]. CagA proteins always possess the EPIYA-A and EPIYA-B sites, but some proteins also contain one or more
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