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      Relationship between the iceA gene of Helicobacter pylori and clinical outcomes

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          Abstract

          Background

          The complex pathogenesis of Helicobacter pylori ( H. pylori) and the features of the host influence the diverse clinical outcomes. A mass of studies about virulence genes have accelerated the exploration of pathogenesis of H. pylori infection. Induced by contact with epithelium gene A ( iceA) is one of the biggest concerned virulence genes. In this study, we explored the relationship between iceA and the magnitude of the risk for clinical outcomes and the prevalence of iceA-positive H. pylori in People’s Republic of China and other countries.

          Methods

          We searched the electronic databases of PubMed, Embase, CNKI, VIP, and Wanfang by literature search strategy. The studies conforming to the inclusion criteria were assessed. With these data, we systematically analyzed the relationship between the iceA gene of H. pylori and clinical outcomes.

          Results

          Nineteen articles with 22 studies, a total of 2,657 cases, were involved in the study. The iceA1 gene was significantly associated with peptic ulcer disease (odds ratio =1.28, 95% confidence interval =1.03–1.60; P=0.03), especially in People’s Republic of China (odds ratio =1.40, 95% confidence interval =1.07–1.83; P=0.01). Moreover, the prevalence of iceA1 was significantly higher than iceA2 in People’s Republic of China ( P<0.0001). The prevalence of both iceA1 and iceA2 was significantly different ( P<0.0001) in People’s Republic of China and in other countries.

          Conclusion

          The system analysis showed that infection with the iceA1-positive H. pylori significantly increased the overall risk for peptic ulcer disease, especially in People’s Republic of China. The iceA2 gene status and clinical outcome of H. pylori infection have no significant correlation. H. pylori iceA1 genotype is the major epidemic strain in People’s Republic of China.

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          Most cited references 32

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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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            Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori.

            Clinical outcome of Helicobacter pylori infection may be associated with specific virulence-associated bacterial genotypes. The aim of this study was to assess the relationships between H. pylori cagA, vacA, and iceA status and severity of disease. Gastric biopsy specimens from 94 patients in The Netherlands were analyzed by polymerase chain reaction and reverse hybridization. cagA was present in 63 (67%) of 94 cases and was associated with peptic ulcer disease (P = 0.0019). vacA geno-types s1a/m1, s1b/m2, s1b/m1, s1b/m2, and s2/m2 were found in 36.2%, 23.4%, 2.1%, 5.3%, and 20.2%, respectively. Ten isolates (10.6%) contained multiple vacA genotypes. The presence of peptic ulcers was associated with type s1 strains (P = 0.0006) but not with the m type (P = 0.2035). cagA and vacA s1 were strongly associated (P < 10(-5)). iceA1 was found in 53 (56.4%) and iceA2 in 25 (26.6%) of the 94 cases. In 14 isolates (14.9%), both iceA alleles were found, and 2 (2.1%) were negative for both iceA1 and iceA2. iceA1 was also associated with peptic ulcer disease (P = 0.0042). The iceA allelic type was independent of the cagA and vacA status. vacA s1, cagA, and iceA1 are markers of H. pylori strains that are more likely to lead to ulcer disease.
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              Helicobacter pylori virulence factors in gastric carcinogenesis.

              Helicobacter pylori infection is the most important risk factor in the development of non-cardia gastric adenocarcinoma; host genetic variability and dietary co-factors also modulate risk. Because most H. pylori infections do not cause cancer, H. pylori heterogeneity has been investigated to identify possible virulence factors. The strongest candidates are genes within the cag (cytotoxin-associated antigen) pathogenicity island, including the gene encoding the CagA protein, as well as polymorphic variation in the VacA vacuolating exotoxin and the blood group antigen binding adhesin BabA. Improved understanding of the pathogenesis of H. pylori-associated gastric cancer may improve risk stratification for prevention and therapy.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2016
                06 July 2016
                : 12
                : 1085-1092
                Affiliations
                [1 ]Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, People’s Republic of China
                [2 ]Department of Microbiology, School of Medicine, Hubei University for Nationalities, Enshi, People’s Republic of China
                [3 ]State Key Laboratory of Oral Diseases, Chengdu, People’s Republic of China
                Author notes
                Correspondence: Baoning Wang, Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, No 17 People’s South Road, Chengdu 610041, People’s Republic of China, Email danial.w@ 123456163.com
                Mingyuan Li, Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, No 17 People’s South Road, Chengdu 610041, People’s Republic of China, Email lmy3985@ 123456sina.com
                Article
                tcrm-12-1085
                10.2147/TCRM.S107991
                4939977
                27462162
                © 2016 Huang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Medicine

                helicobacter pylori, icea, gastritis, peptic ulcer disease, gastric carcinoma

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