Genotyping of Helicobacter pylori shows high diversity of strains circulating in central Vietnam

Abstract

In Vietnam, the high prevalence of Helicobacter pylori infection represents a serious health problem. Virulence genes of H. pylori have been associated to increased risk of severe gastrointestinal diseases and the genetic background differs in geographical areas. We investigated cagA and vacA genotypes of H. pylori from dyspeptic patients from central Vietnam and the correlation with clinical outcomes; we also performed sequencing analysis of partial cagA gene. Overall, 84% of strains were cagA-positive, 75% were East-Asian type with a prevalence of vacAs1i1m1 and vacAs1i1m2 genotypes (66.7% and 33.3%, respectively) and 9% were Western type vacAs1i1m1 (n=4) and vacAs1i1m2 (n=4); vacAs1i2m2 (n=4) and vacAs2i2m2 (n=2) genotypes were associated to cagA-negative. Strains from gastric ulcer and cancer were of East-Asian type, while cagA-negative or Western strains were from gastritis and duodenal ulcer. H. pylori strains from gastric ulcer patients were predominantly vacAs1i1m1 compared to other vacA genotypes (p<0.05). East-Asian type strains vacAs1i1m1 or vacAs1i1m2 were found in gastric cancer patients and also in less severe disease. Phylogenetic tree analysis of CagA sequences showed the co-circulation of H. pylori of different geographical origins with Western sequences closer related to Cambodia, one of the entry of Western strains in Southeast-Asia through human migrations. Sequence analysis revealed in two Western type strains a chimeric CagA-3' region with identity with East-Asian CagA suggesting recombination event in the process of evolution among East-Asian and Western H. pylori strains. Moreover, polymorphism in CagA multimerization (CM) motif was observed including new East-Asian CM motifs. In conclusion, we have found in central Vietnam a geographically dependent diversity of cagA genotype, with higher rates of cagA-negative and Western-type strains compared with other nation's parts that can partly explain the lower risk of gastric cancer. The polymorphism of CM motifs may explain the variability of disease manifestations of vacAs1i1m1 and s1i1m2 East-Asian isolates.

Keywords: CM polymorphism; Chimeric CagA; Helicobacter pylori; cagA; vacA.