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      High Frequency of vacA s1m2 Genotypes Among Helicobacter pylori Isolates From Patients With Gastroduodenal Disorders in Kermanshah, Iran

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          Abstract

          Background:

          Helicobacter pylori infection and related diseases outcome are mediated by a complex interplay between bacterial, host and environmental factors. Several distinct virulence factors of H. pylori have been shown to be associated with different clinical outcomes. Here we focused on vacA and cagA genotypes of H. pylori strains isolated from patients with gastric disorder.

          Objectives:

          The aim of this study was to determine the frequency of two toxins and genotypes of VacA toxin in patients referred to a central hospital in the west of Iran (Imam Reza hospital, Kermanshah) during 2011 - 2012.

          Patients and Methods:

          Samples were collected from patients infected with H. pylori. Gastric biopsy specimens from the stomach antrum and corpus were cultured. PCR analysis was performed for genotyping H. pylori vacA and cagA genes.

          Results:

          Helicobacter pylori was isolated from 48% (96/200) of patients with gastroduodenal disorders. In 81/96 (84%) cases, the cagA gene was present. Among different genotypes of vacA, two s1m2 and s2m2 genotypes were dominant with frequency of 39.5% and 50%, respectively. The frequency of the s1m1 genotype was 7.2% (7/96), which is much lower than elsewhere. H. pylori isolates with positive results for cagA gene and vacA s1m2 genotypes showed statistically significant correlation with peptic ulcer ( s1m2 13/34 [38.2%] P = 0.003). However, isolates of H. pylori infection with cagA gene and vacA s2m2 genotypes were significantly associated with development of gastritis ( s2m2 41/42 [97.6%] P = 0.000).

          Conclusions:

          About 90% of H. pylori strains potentially contained vacA s2m2 and s1m2 genotypes. Infection with H. pylori strain containing the cagA gene or the vacA s1m1 and s1m2 genotypes was associated with increased incidence of peptic ulcer disease (PUD).

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          Most cited references40

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          Oncogenic mechanisms of the Helicobacter pylori CagA protein.

          Infection with strains of Helicobacter pylori that carry the cytotoxin-associated antigen A (cagA) gene is associated with gastric carcinoma. Recent studies have shed light on the mechanism through which the cagA gene product, CagA, elicits pathophysiological actions. CagA is delivered into gastric epithelial cells by the bacterial type IV secretion system, where it deregulates the SHP2 oncoprotein. Intriguingly, CagA is noted for its variation, particularly at the SHP2-binding site, which could affect the potential of different strains of H. pylori to promote gastric carcinogenesis.
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            Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration.

            Approximately 50% of Helicobacter pylori strains produce a cytotoxin, encoded by vacA, that induces vacuolation of eukaryotic cells. Analysis of a clinically isolated tox- strain (Tx30a) indicated secretion of a 93-kDa product from a 3933-base pair vacA open reading frame. Characterization of 59 different H. pylori isolates indicated the existence of three different families of vacA signal sequences (s1a, s1b, and s2) and two different families of middle-region alleles (m1 and m2). All possible combinations of these vacA regions were identified, with the exception of s2/m1 (p < 0.001); this mosaic organization implies that recombination has occurred in vivo between vacA alleles. Type s1/m1 strains produced a higher level of cytotoxin activity in vitro than type s1/m2 strains; none of 19 type s2/m2 strains produced detectable cytotoxin activity. The presence of cagA (cytotoxin-associated gene A) was closely associated with the presence of vacA signal sequence type s1 (p < 0.001). Among patients with past or present peptic ulceration, 21 (91%) of 23 harbored type s1 strains compared with 16 (48%) of 33 patients without peptic ulcers; only 2 (10%) of 19 subjects harboring type s2 strains had past or present peptic ulcers (p < 0.005). Thus, specific vacA genotypes of H. pylori strains are associated with the level of in vitro cytotoxin activity as well as clinical consequences.
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              Relationship between Helicobacter pylori iceA, cagA, and vacA status and clinical outcome: studies in four different countries.

              There is continuing interest in identifying Helicobacter pylori virulence factors that might predict the risk for symptomatic clinical outcomes. It has been proposed that iceA and cagA genes are such markers and can identify patients with peptic ulcers. We compared H. pylori isolates from four countries, looking at the cagA and vacA genotypes, iceA alleles, and presentation of the infection. We used PCR to examine iceA, vacA, and cagA status of 424 H. pylori isolates obtained from patients with different clinical presentations (peptic ulcer, gastric cancer, and atrophic gastritis). The H. pylori isolates examined included 107 strains from Bogota, Colombia, 70 from Houston, Tex., 135 from Seoul, Korea, and 112 from Kyoto, Japan. The predominant genotype differed among countries: the cagA-positive iceA1 vacA s1c-m1 genotype was predominant in Japan and Korea, the cagA-positive iceA2 vacA s1b-m1 genotype was predominant in the United States, and the cagA-positive iceA2 vacA s1a-m1 genotype was predominant in Colombia. There was no association between the iceA, vacA, or cagA status and clinical outcome in patients in the countries studied. iceA status shows considerable geographic differences, and neither iceA nor combinations of iceA, vacA, and cagA were helpful in predicting the clinical presentation of an H. pylori infection.
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                Author and article information

                Journal
                Jundishapur J Microbiol
                Jundishapur J Microbiol
                10.5812/jjm
                Kowsar
                Jundishapur Journal of Microbiology
                Kowsar
                2008-3645
                2008-4161
                22 November 2015
                November 2015
                : 8
                : 11
                : e25425
                Affiliations
                [1 ]Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
                [2 ]Department of Internal Medicine, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
                [3 ]Department of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany
                [4 ]Department of Epidemiology, Epidemiology of Cancer, Kermanshah University of Medical Sciences, Kermanshah, IR Iran
                Author notes
                [* ]Corresponding author: Ramin Abiri, Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, P. O. Box: 6714869914, Kermanshah, IR Iran. Tel: +98-9122773648, Fax: +98-8314274623, E-mail: ramin_abiri@ 123456yahoo.com
                Article
                10.5812/jjm.25425
                4740511
                26862378
                278a76ab-1fcc-4c76-978f-b42fd8178075
                Copyright © 2015, Ahvaz Jundishapur University of Medical Sciences.

                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.

                History
                : 18 November 2014
                : 05 February 2015
                : 13 April 2015
                Categories
                Research Article

                peptic ulcer,helicobacter pylori,caga,vaca
                peptic ulcer, helicobacter pylori, caga, vaca

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