Evolutionary Dynamics of Helicobacter pylori cagA and vacA Genes in Iran and their Association with Clinical Outcomes

Abstract

Background: There is a relationship between specific genotypes of Helicobacter pylori cagA and vacA genes and the increased risk of peptic ulcer diseases and gastric cancer. These genes also possess strong patterns of geographical differentiation. The present study aims to determine the patterns of variation of the virulence genes in Iran and their association with clinical status.Materials and Methods:Sequence fragments for cagA and vacA were obtained from a total of 147 H. pylori isolates from diverse geographical and ethnic sources within Iran. We used phylogenetic methods to determine the patterns of allelic diversity, and the relationship between evolutionary lineages and clinical status.Results:Phylogenetic analyses of Iranian cagA gene disclosed four lineages, whereas the vacA gene had two distinct lineages. The cagA lineage II showed extensive genetic diversity compared with lineage I. cagA lineages III and IV disclosed mixed ancestries with recombinant nucleotides that originated from lineages I and II. Iranian strains with vacA lineage II genotype were significantly cagA+ (> 90%, p = 0.0) and correlated with a higher rate of peptic ulcers in infected individuals (p =0.003). Most strains in the cagA lineage I showed a vacA lineage II genotype (p = 0.003) and significantly correlated with an increased risk of peptic ulcers in infected individuals (p = 0.022). Strains with cagA lineage III genotype significantly correlated with gastritis (p = 0.0).Conclusion:The increased level of allelic diversity in the virulence genes shows strong evolutionary dynamics, resulting in the emergence of new clonal genealogies of the cagA gene within Iran. Particular lineages of the Iranian cagA and vacA genes correlate with peptic ulcer diseases.