Functional Cytotoxin Associated Gene A in Helicobacter pylori Strains and Its Association with Integrity of Cag-pathogenicity Island and Histopathological Changes of Gastric Tissue

Abstract

Objectives: Existence of cytotoxin associated gene A (cagA) is considered as a marker for detection of an oncogenic Helicobacter pylori strain. Expression of cagA in the strains with incomplete delivery system (partial CagPAI) could convert them to less virulent strains. This study was aimed to analyze expression of cagA in H. pylori strains presenting diverse cagPAI and its effect on histopathological changes of the gastric tissue. Methods: Clinical strains of H. pylori and related histopathological data were obtained to examine the presence of 12 cagPAI segments by PCR. Expression of cagA was analyzed by RT-PCR as well as Immunoblotting on RNA and protein extracts of the cagPAI-positive strains, respectively. In situe expression of CagA-positive strains was determined in a gastric epithelial cell line. Results: Intact cagPAI was detected among 33% (4/12) of H. pylori strains. Out of 7 diverse cagPAI genotypes in these strains, expression of cagA was confirmed in 2 strains with complete cagPAI at both RNA and protein levels. Occurrence of intestinal metaplasia and severe active gastritis were mainly detected in the strains with complete cagPAI genotype. No association was detected between EPIYA types of the strains and expression of cagA. Conclusions: These results collectively showed high diversity of cagA and cagPAI among the H. pylori strains. These diversities may provide some reasons to explain distinct disease severity caused by different H. pylori strains in the gastric tissue.