Association of Helicobacter pylori vacA genotypes and peptic ulcer in Iranian population: a systematic review and meta-analysis

Keikha, Masoud; Ali‐Hassanzadeh, Mohammad

doi:10.1186/s12876-020-01406-9

Cited by 30 publications

(21 citation statements)

References 82 publications

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“…So far, several vacA genotypes are distinguished including s1, s2, m1, m2, s1m1, s1m2, s2m2, and s2m1. The VacA s1 genotype is one of the most abundant in H. pylori -infected patients and there is an association between this genotype and peptic ulcer disease [ 85 ]. VacA s1m1 is commonly found in H. pylori -infected patients with chronic gastritis, whereas in H. pylor i-induced gastric cancer, usually s1 and m1 VacA genotypes are most prevalent [ 86 , 87 ].…”

Section: Vacuolating Cytotoxin Amentioning

confidence: 99%

Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

Baj

Forma

Sitarz

et al. 2020

Cells

176

100

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Gastric cancer constitutes one of the most prevalent malignancies in both sexes; it is currently the fourth major cause of cancer-related deaths worldwide. The pathogenesis of gastric cancer is associated with the interaction between genetic and environmental factors, among which infection by Helicobacter pylori (H. pylori) is of major importance. The invasion, survival, colonization, and stimulation of further inflammation within the gastric mucosa are possible due to several evasive mechanisms induced by the virulence factors that are expressed by the bacterium. The knowledge concerning the mechanisms of H. pylori pathogenicity is crucial to ameliorate eradication strategies preventing the possible induction of carcinogenesis. This review highlights the current state of knowledge and the most recent findings regarding H. pylori virulence factors and their relationship with gastric premalignant lesions and further carcinogenesis.

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Section: Vacuolating Cytotoxin Amentioning

confidence: 99%

Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

Baj

Forma

Sitarz

et al. 2020

Cells

176

100

View full text Add to dashboard Cite

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“…Finally, it should be noted that our study had several limitations including a high degree of heterogeneity in the analysed studies, limitations in the number of studies, publication bias and lack of correlation between cagA genotypes and other virulence factors with the development of gastrointestinal diseases. Many studies have shown that the coexistence of some cagA and vacA gene alleles increases the risk of gastric cancer in different populations around the world [ 87 , 91 , 92 ]. Therefore, further studies are needed to elucidate the predominant role of cagA genotypes in assessing the frequency of gastrointestinal diseases.…”

Section: Discussionmentioning

confidence: 99%

EPIYA motifs of Helicobacter pylori cagA genotypes and gastrointestinal diseases in the Iranian population: a systematic review and meta-analysis

Keikha

2021

New Microbes and New Infections

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Helicobacter pylori is one of the best risk factors for gastric cancer. Recent studies have examined the relationship between virulence factors, in particular CagA toxin, and the development of gastrointestinal diseases. According to the literature, there is a significant relationship between the polymorphism of cagA -EPIYA motifs and progression to severe clinical outcomes. The main goal of our study was to determine the possible association between cagA genotypes and the risk of severe clinical outcomes in the Iranian population. We investigated these ambiguities using a comprehensive meta-analysis study, in which we evaluated data from 1762 Iranian patients for a potential correlation between all cagA gene genotypes and gastrointestinal diseases. According to statistical analysis, the frequencies of cagA genotypes including ABC, ABCC, AB and ABCCC in the Iranian population were estimated at 80.18%, 22.81%, 5.52% and 2.76%, respectively; the ABD genotype was not detected in these PCR-based studies. There was a significant relationship between cagA genotypes ABCC and ABCCC and severe clinical outcomes of infection such as peptic ulcer and gastric cancer. Overall, it can be concluded that there is a positive correlation with the number of copies of EPIYA-C and the increase of gastric cancer. Therefore, according to our results, it seems that the EPIYA-ABCCC motif has a strong positive relationship with gastric cancer in the Iranian population.

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“…Full-length sequence analysis of the vacA gene showed that this gene has a mosaic structure and is encoded by different subfamilies s1, m1 and m2 alleles, with its own biological activities [ 11 ]. The vacA s1/m1 genotype possess the highest toxicity property for host cells, while the vacA s2/m2 genotype biologically is inactive [ 12 , 13 ]. CagA is encoded by cagA gene; this toxin is highly immunogenic, and upon entering the host cell, it activates kinases through EPIYA motifs in its C-terminal, which in turn disrupt signaling pathways [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical relevance of the cagA and vacA s1m1 status and antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis

2022

Self Cite

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Background The role of Helicobacter pylori (H. pylori) virulence factors of such as vacA s1m1 and cagA in designating clinical outcomes and eradication rate has been deeply challenged in the last decade. The goal of this analysis was to identify the potential relevance between cagA and vacA genotypes with reported antibiotic resistance observed in clinical H. pylori isolates. Methods This literature search was conducted in databases such as Clarivate analytics, PubMed, Scopus, EMBASE, DOAJ, and Google Scholar by April 2022, regardless of language restrictions and publication date. Quality of the included studies was assessed by the Newcastle–Ottawa scale. Statistical analysis of retrieved studies was fulfilled using Comprehensive Meta-Analysis software version 2.2. Following quality appraisal of eligible studies, potential association between the status of cagA and vacA genes with resistance to clarithromycin, metronidazole, amoxicillin, tetracycline, and levofloxacin was measured using odds ratio with 95% confidence interval. We also used sensitivity analyses and meta-regression to eliminate the source of heterogeneity from the overall estimates. Publication bias was assessed using funnel plot, Egger’s test, Begg’s test with the trim and fill procedure to assess the presence and magnitude of publication bias in the included studies. Results Our findings suggested that a significant relationship between cagA status ‎and increase resistance ‎to metronidazole (OR: 2.69; 95% CI: 1.24–5.83‎‏‎). In subgroup analysis, we ‎found that in the Western ‎population, infection with cagA-positive strains could be led to increase in ‎the resistance to ‎metronidazole (OR: 1.59; 95% CI: ‎0.78–3.21‎‏‎), ‎amoxicillin (OR: ‎19.68‎; 95% CI: 2.74–‎‎141.18), ‎and ‎levofloxacin (OR: ‎11.33; 95% CI: ‎1.39–‎‎91.85). After implementation of trim and fill method, the adjusted OR was not significantly differed from original estimates which in turn represented our subgroup analysis was statistically robust. On the other hand, vacA ‎genotypes usually ‎reduce the antibiotic resistance of this bacterium, so that vacA s1m1 significantly reduces the ‎resistance to ‎metronidazole (OR: 0.41; 95% CI: 0.20–0.86‎‏‎). Surprisingly, resistance of vacA s2m2 strains to antibiotics was low, the reason may be due ‎to the non-inflammatory properties of strains containing vacA s2m2. The meta-regression and sensitivity analyses successfully reduced the effect of heterogeneity from the overall estimates. In addition, although the pooled OR is reduced after trim and fill adjustment but results do not change the conclusion regarding vacA genotypes and antibiotic resistance. Conclusions According to our findings, it was clearly demonstrated that cagA-positive strains are resistance to metronidazole, especially in Western countries. In Western countries, vacA s1m1 increases resistance to amoxicillin and levofloxacin. Based on the present findings, the vacA s1m1 genotype significantly increases resistance to metronidazole, while the vacA s1m2 decreases resistance to clarithromycin and metronidazole. Resistance to antibiotics in less virulent (vacA s2m2) strains is statistically significant lower than others.

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Association of Helicobacter pylori vacA genotypes and peptic ulcer in Iranian population: a systematic review and meta-analysis

Cited by 30 publications

References 82 publications

Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

EPIYA motifs of Helicobacter pylori cagA genotypes and gastrointestinal diseases in the Iranian population: a systematic review and meta-analysis

Clinical relevance of the cagA and vacA s1m1 status and antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis

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