Genotypic diversity of the Helicobacter pylori vacA c region and its correlation with gastric disease outcomes

<b>Introduction</b> <i>. Helicobacter pylori</i> infection is a major cause of peptic ulcer and gastric adenocarcinoma. The infection progression to severe diseases depends on several factors, including bacterial ones. CagA and VacA are two major virulence factors widely studied and implicated in <i>H. pylori</i> diseases.<b>Gap statement.</b> Although the allelic prevalence of the s, m, i and d regions of the <i>H. pylori vacA</i> gene and their relation with gastric disease outcomes have been largely studied, there is a gap in knowledge regarding the prevalence and the association of the <i>vacA</i> c region with those pathologies. This polymorphic region could exhibit a large variability which might impact the virulence of the bacterium and the severity of gastric damage.<b>Aim.</b> The aim of this study was to investigate the prevalence of <i>H. pylori vacA</i> c alleles and to assess the association of <i>vacA</i> mosaicism with gastric damage in a large Moroccan population.<b>Methodology.</b> <i>H. pylori</i> positive gastric biopsies, obtained in 709 consenting patients who consulted the gastroenterology department of the Hassan II University Hospital of Fez (Morocco) for clinical endoscopy, between 2009 and 2019, were used in this study. DNA extracted from the biopsy samples was used to determine the <i>vacA</i> c genotype using specific PCRs. <i>H. pylori cagA</i>, <i>vacA</i> s, <i>vacA</i> m, <i>vacA</i> d and <i>vacA</i> i genotypes of these samples were previously determined.<b>Results.</b> The <i>vacA</i> c2 genotype was detected in 44.7% of samples and the <i>vacA</i> c1 genotype in 16.5% of cases. Multiple infections (detection of the two <i>vacA</i> c allelic forms) were obtained in 9% of samples. Correlation of <i>H. pylori vacA</i> c genotype with pathologies showed that the <i>vacA</i> c1 allele was strongly associated with the risk of gastric cancer (GC) [odds ratio=3.14, confidence intervals 95% (1.08-9.09)].<b>Conclusion.</b> The results of this study confirm that despite the large <i>H. pylori</i> genetic diversity, the genotypic distribution is marked by a predominance of the less virulent strains in Morocco. Also, even if <i>vacA</i> allelic combinations seem to impact the toxicity of this bacterium, patients infected with <i>H. pylori vacA</i> c1 genotype are more likely to develop GC than those infected by <i>H. pylori vacA</i> c2 genotype.