Helicobacter pylori vacA genotyping in relation to cagA status, ultra-structure of gastric mucosa and clinical outcomes in Egyptian patients

Abstract

Helicobactor pylori (H. pylori) has been strongly associated with gastritis, peptic ulcer and is linked to an increased risk of gastric cancer. The cytotoxin-associated gene product (cagA) and the vacuolating cytotoxin (vacA) have been implicated as two major virulence factors of H. pylori. Since there is an increasing evidence that genetic variability of H. pylori may have clinical importance, we aimed to evaluate different vacA genotypes and reveal its relationship with endoscopic and transmission electron microscopy (TEM) findings among H. pylori infected Egyptian patients. Forty H. pylori infected patients possessing vacA gene who underwent upper endoscopic examination were considered to be infected with H. pylori when rapid urease test and detection of 16S rRNA in gastric biopsy recorded positive. Both vacA and cagA genotypes were detected by polymerase chain reaction (PCR). The TEM was performed to assess the ultra-structure of the gastric mucosa. Four vacA genotypes were identified, the most prominent was the s2/m2 allele combination (52.5%) followed by s1/m1 (27.5%), s1/m2 (17.5%) and s2/m1 genotype was found just in one H. pylori strain (2.5%). There were significant correlations between vacA s2/m2 and gastritis (65.2%), and vacA s1/m1 and peptic ulceration (57%). The cagA gene was associated with 38% of vacA genotypes and 60% of which were significantly associated with vacA s1/m1 genotype with the development of severe gastritis reaching up to gastric ulcer. The TEM revealed H. pylori spiral and coccoid forms, cytoplasmic vacuolar degeneration caused by vacA, swollen mitochondria and dilated rough endoplasmic reticulum. In Egypt where prevalence of H. pylori infection is high, genotyping of H. pylori virulence factors can help to predict patients who are at a high risk of related gastroduodenal diseases. Although H. pylori with vacA s2/m2 genotype is mostly related to low level of virulent strains yet, significant crosstalk between H. pylori strains harboring both vacA s1/m1 and cagA gene provides crucial insights into virulence of high level.