Abstract

BackgroundChronic gastritis, peptic ulcer disease, and gastric cancer have been shown to be related to infection with Helicobacter pylori (H. pylori). Two major virulence factors of H. pylori, CagA and VacA, have been associated with these sequelae of the infection. In this study, total DNA was isolated from gastric biopsy specimens to assess the cagA and vacA genotypes.ResultsVariations in H. pylori cagA EPIYA motifs and the mosaic structure of vacA s/m/i/d regions were analysed in 155 H. pylori-positive gastric biopsies from 71 individuals using PCR and sequencing. Analysis of a possible association between cagA and vacA genotypes and gastroduodenal pathogenesis was made by logistic regression analysis. We found that H. pylori strains with variation in the number of cagA EPIYA motif variants present in the same biopsy correlated with peptic ulcer, while occurrence of two or more EPIYA-C motifs was associated with atrophy in the gastric mucosa. No statistically significant relation between vacA genotypes and gastroduodenal pathogenesis was observed.ConclusionsThe results of this study indicate that cagA genotypes may be important determinants in the development of gastroduodenal sequelae of H. pylori infection. In contrast to other studies, vacA genotypes were not related to disease progression or outcome. In order to fully understand the relations between cagA, vacA and gastroduodenal pathogenesis, the mechanisms by which CagA and VacA act and interact need to be further investigated.

Highlights

  • Chronic gastritis, peptic ulcer disease, and gastric cancer have been shown to be related to infection with Helicobacter pylori (H. pylori)

  • H. pylori is a microaerophilic, spiral shaped Gram-negative bacterium that chronically infects the gastric mucosa [1]. It is recognised as a human pathogen associated with chronic gastritis [1], peptic ulcer [2] and gastric cancer [3], the development of which are related to the virulence factors cytotoxin associated antigen (CagA) [4,5] and vacuolating cytotoxin A [6,7]

  • Analysis of cagA EPIYA motifs A total of 155 gastric biopsy specimens from 71 individuals were analysed for cagA EPIYA genotypes

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Summary

Introduction

Peptic ulcer disease, and gastric cancer have been shown to be related to infection with Helicobacter pylori (H. pylori). H. pylori is a microaerophilic, spiral shaped Gram-negative bacterium that chronically infects the gastric mucosa [1] It is recognised as a human pathogen associated with chronic gastritis [1], peptic ulcer [2] and gastric cancer [3], the development of which are related to the virulence factors cytotoxin associated antigen (CagA) [4,5] and vacuolating cytotoxin A (vacA) [6,7]. CagA localises to the inner surface of the plasma membrane and becomes phosphorylated on specific tyrosine residues within repeating penta amino acid Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs present at the C-terminus of the protein [18,19,20]. This is supported by a higher risk of cancer development in strains with a high degree of phosphorylation [28]

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