Multiple repeats of Helicobacter pylori CagA EPIYA-C phosphorylation sites predict risk of gastric ulcer in Iran

Jahromy, Sahar Honarmand; Siavoshi, Farideh; Malekzadeh, Reza; Sattari, Taher Nejad; Latifi‐Navid, Saeid

doi:10.1016/j.micpath.2015.09.005

Cited by 18 publications

(11 citation statements)

References 46 publications

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“…Indeed, our prior study showed a significant association between infection with H. pylori strains carrying the EPIYA-ABD cagA genotype and the development of gastric cancer (23). Similarly, other studies have shown that CagA variants containing an increased number of EPIYA-C motifs correlate to more virulent disease characteristics (15, 24, 25). …”

Section: Introductionmentioning

confidence: 55%

“…Multiple copies of cagA appeared only in strains carrying no or single EPIYA-C motifs. Since CagA variants containing an increased number of EPIYA-C motifs are known to correlate with more virulent disease characteristics (15, 24, 25), carriage of multiple copies of cagA in strains containing the AB or ABC motifs might provide a mechanism to compensate for the decreased virulence abilities of those CagA variants. Thus, the dynamic expansion and contraction of cagA copy number may serve as a novel mechanism by which H. pylori modulates gastric disease development.…”

Section: Discussionmentioning

confidence: 99%

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Dynamic Expansion and Contraction ofcagACopy Number inHelicobacter pyloriImpact Development of Gastric Disease

Jang

Blum

et al. 2017

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Infection with Helicobacter pylori is a major risk factor for development of gastric disease, including gastric cancer. Patients infected with H. pylori strains that express CagA are at even greater risk of gastric carcinoma. Given the importance of CagA, this report describes a new molecular mechanism by which the cagA copy number dynamically expands and contracts in H. pylori. Analysis of strain PMSS1 revealed a heterogeneous population in terms of numbers of cagA copies; strains carried from zero to four copies of cagA that were arranged as direct repeats within the chromosome. Each of the multiple copies of cagA was expressed and encoded functional CagA; strains with more cagA repeats exhibited higher levels of CagA expression and increased levels of delivery and phosphorylation of CagA within host cells. This concomitantly resulted in more virulent phenotypes as measured by cell elongation and interleukin-8 (IL-8) induction. Sequence analysis of the repeat region revealed three cagA homologous areas (CHAs) within the cagA repeats. Of these, CHA-ud flanked each of the cagA copies and is likely important for the dynamic variation of cagA copy numbers. Analysis of a large panel of clinical isolates showed that 7.5% of H. pylori strains isolated in the United States harbored multiple cagA repeats, while none of the tested Korean isolates carried more than one copy of cagA. Finally, H. pylori strains carrying multiple cagA copies were differentially associated with gastric disease. Thus, the dynamic expansion and contraction of cagA copy numbers may serve as a novel mechanism by which H. pylori modulates gastric disease development.

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Section: Introductionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Dynamic Expansion and Contraction ofcagACopy Number inHelicobacter pyloriImpact Development of Gastric Disease

Jang

Blum

et al. 2017

mBio

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“…It seems that circulating strains among Iranian patients originate from hpEurope strains, and have transferred to Iran from some groups such as Arabs in the 7-8th centuries, Uzbeks ght in 16th century, and Ottoman Empire during the 20th century (86). Existence of cagA2a genotype (EPIYA-ABC motifs) in Iran's studies con rm this hypothesis (37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). However, why the number of gastric cancer cases in Iran is as high as cases of Japan, South Korea, and China?…”

Section: Discussionmentioning

confidence: 93%

“…In general, cagA genotypes recognized from around the world include AB, ABC, ABCC, ABCCC, ABCCCC, and ABD. In studies from Iran, so far there is no any document based on detection of cagA genotypes ABCCCC and ABD, which is arising from genetic differences between isolated strains of Iranian patients and East Asian's strains (37)(38)(39)(40)(41)(42)(43)(44)(45)(46). Nevertheless, according to studies, in Iran, cagA genotypes ABCC and ABCCC are more prevalent in peptic ulcer and gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

What is the Relationship Between Helicobacter Pylori CagA Genotypes and Gastrointestinal Diseases in the Iranian Population? A Systematic Review and Meta-Analysis

Keikha¹

2020

Preprint

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Background: Helicobacter pylori (H. pylori) is one of the most well-known risk factors for getting the gastric cancer disease. In recent studies, the relationship between its virulence factors, specially CagA (cytotoxin‐associated gene A) toxin and development into the gastrointestinal diseases is taken into consideration. According to review of literature, despite the presence of four motifs A, B, C, and D in CagA toxin, two motifs C and D are more associated with gastrointestinal complications in patients who are infected by H. pylori. Methods: In the present study, we researched about theses ambiguities using a comprehensive meta-analysis study. In this study, we assessed the information of 1762 Iranian patients for potential relationship between all genotypes of cagA gene and gastrointestinal diseases.Results: According to statistical analysis, the abundance of cagA genotypes AB, ABC, ABCC, ABCCC, and ABD in Iranian population is 5.52%, 80.18%, 22.81%, 2.76%, and 0% respectively. In addition, it was determined that there is a significant relationship between cagA genotypes ABCC and ABCCC on the one hand and cagA genotype ABCCC on the other hand with susceptibility to chronic gastritis and gastric cancer respectively.Conclusions: Overall, it can be concluded that the higher number of EPIYA-C copy numbers lead to the higher risk of gastric cancer. According to our results, it seems that the presence of EPIYA-ABCCC motif in strains of H. pylori should be considered as an appropriate marker in preventing the gastric cancer among the Iranian population.

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“…The pathogenesis of gastric ulcer has not been studied thoroughly; however, weakening of protection effect caused by Helicobacter pylori (HP) infection and excessive secretion of gastric acid has been agreed. 5 , 6 Treatment with drugs such as acid inhibitors (prilosec and lansoprazole), anti-inflammatory drugs (levofloxacin and amoxicillin) and gastric mucosal protective agents (bismuth potassium citrate) were the main therapy for gastric ulcer induced bleeding previously. Though drug treatment has certain efficacy, it fails to control rebleeding.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Endoscopy in Combination with Quadruple Therapy in Treating Bleeding Caused by Gastric Ulcer

et al. 2018

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Objective:To analyze the efficacy of therapeutic endoscopy in combination with quadruple therapy in treating bleeding caused by gastric ulcer and investigate the factors inducing rebleeding.Methods:Two hundred and twelve patients with bleeding caused by gastric ulcer who were admitted to Binzhou People's Hospital, Shandong, China between April 2015 and April 2016 were selected as research subjects. The patients were randomly divided into a control group and an experimental group. Patients in the control group were treated by quadruple therapy, while patients in the observation group received therapeutic endoscopy treatment in addition to the same treatment as the control group. The treatment efficacy, adverse reaction, H pylori (Hp) clearance rate and rebleeding were compared between the two groups.Results:The effective rate of the observation group was 98.1%, which was significantly higher than that of the control group (80.2%), and the difference had statistical significance (P<0.05). The incidence of adverse reactions in the observation group was lower than that in the control group. The Hp clearance rate of the observation group was higher than that of the control group, and the difference had statistical significance (P<0.05). The multi-factor analysis on rebleeding suggested that whether therapeutic endoscopy was performed or not, hemoglobin level and presence of peptic ulcer stage A1 were independent risk factors.Conclusion:Endoscopic treatment in combination with quadruple therapy is better in the treatment of bleeding caused by gastric ulcer as compared to medical treatment alone. Patients with high-risk factors such as low content of hemoglobin and ulcer at stage A1 should be monitored more carefully to prevent the occurrence of rebleeding.

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Multiple repeats of Helicobacter pylori CagA EPIYA-C phosphorylation sites predict risk of gastric ulcer in Iran

Cited by 18 publications

References 46 publications

Dynamic Expansion and Contraction ofcagACopy Number inHelicobacter pyloriImpact Development of Gastric Disease

Dynamic Expansion and Contraction ofcagACopy Number inHelicobacter pyloriImpact Development of Gastric Disease

What is the Relationship Between Helicobacter Pylori CagA Genotypes and Gastrointestinal Diseases in the Iranian Population? A Systematic Review and Meta-Analysis

Therapeutic Endoscopy in Combination with Quadruple Therapy in Treating Bleeding Caused by Gastric Ulcer

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