Arch Clin Infect Dis. 2017 July; 12(3):e62955. Published online 2017 July 31. doi: 10.5812/archcid.62955. Research Article Functional Cytotoxin Associated Gene A in Helicobacter pylori Strains and Its Association with Integrity of Cag -pathogenicity Island and Histopathological Changes of Gastric Tissue Zeinab Fazeli, 1 Masoud Alebouyeh, 2,3,* Mostafa Rezaei Tavirani, 1,** Abbas Yadegar, 2 Nastaran Farzi, 2 and Mohammad Reza Zali 2,3 1 Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2 Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran 3 Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran * Corresponding author: Dr. Masoud Alebouyeh, PhD of Medical Bacteriology, Food Borne and Waterborne Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Tel: +98-2122432518, Fax: +98-2122432517, E-mail: masoud.alebouyeh@gmail.com ** Corresponding author: Dr. Mostafa Rezaei Tavirani, Professor of Biophysics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Tel: +98-2122815616, Fax: +98-2122815601, E-mail: rezaei.tavirani@ibb.ut.ac.ir Received 2016 August 09; Revised 2017 February 17; Accepted 2017 March 14. 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 seg- ments 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. Keywords: Histopathological Changes, Helicobacter pylori, cagPAI 1. Background Helicobacter pylori (H. pylori), a Gram-negative bacterial pathogen, is recognized as an important risk factor for chronic active gastritis, peptic ulcer, gastric cancer, and gastric mucosa associated lymphoid tissue lymphoma (1- 4). Approximately half of the world’s population is in- fected with H. pylori; however, most of the infected people have no symptoms (3, 5). Although initial colonization of this bacterium occurs in early years of life, occurrence of disease depends on its genetic entity and virulence prop- erty in association with host and environmental risk fac- tors (6). Diversity of H. pylori strains was demonstrated in several studies and in different populations (7-10). Associa- tion of this diversity with the severity of gastric disorders was shown for some structural and functional proteins of H. pylori (5, 8, 11, 12). Cag-pathogenicity Island (Cag-PAI) is one of the com- plex genetic structures in bacteria that encodes approx- imately 27 to 31 genes (13-15). While involvement of this structure in inflammation of gastric tissue and its role for delivery of CagA oncoprotein into gastric epithelial cells were demonstrated, there is very few data regarding its as- sociation with the clinical outcome of the infection (5, 6). At least 17 out of 27 cagPAI genes encode main structural proteins that are important for providing a putative type Copyright © 2017, Archives of Clinical Infectious Diseases. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.