Helicobacter pylori CagA EPIYA-C motifs and gastric diseases in Moroccan patients

Khadir, Mounia El; Boukhris, Samia Alaoui; Benajah, Dafr-Allah; Ibrahimi, Sidi Adil; Chbani, Laïla; Bouguenouch, Laila; Rhazi, Karima El; Abkari, M. El; Nejjari, Chakib; Mahmoud, Mustapha; Bennani, Bahia

doi:10.1016/j.meegid.2018.09.015

Cited by 19 publications

(27 citation statements)

References 48 publications

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“…Multiple EPIYA-C repeats cause stronger binding of CagA to SHP-2 than a single EPIYA-C. Multiple EPIYA C repeats are associated with a higher risk of GC[ 34 , 35 ]. The functionality of CagA is increased with multiple EPIYA-C phosphorylation sites and is involved in cellular phenotypic changes.…”

Section: Discussionmentioning

confidence: 99%

Association between human leukocyte antigen gene polymorphisms and multiple EPIYA-C repeats in gastrointestinal disorders

Sarıbaş

Demiryas

Yılmaz

et al. 2020

WJG

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BACKGROUND Polymorphisms of human leukocyte antigen (HLA) genes are suggested to increase the risk of gastric cancer (GC). AIM To investigate the HLA allele frequencies of patients with GC relative to a control group in terms of CagA+ multiple (≥ 2) EPIYA-C repeats. METHODS The patient group comprised 94 patients [44 GC and 50 duodenal ulcer (DU) patients], and the control group comprised 86 individuals [(50 non-ulcer dyspepsia patients and 36 people with asymptomatic Helicobacter pylori ( H. pylori )]. Polymerase chain reaction was performed for the amplification of the H. pylori cagA gene and typing of EPIYA motifs. HLA sequence-specific oligonucleotide (SSO) typing was performed using Lifecodes SSO typing kits (HLA-A, HLA-B HLA-C, HLA-DRB1, and HLA-DQA1-B1 kits). RESULTS The comparison of GC cases in terms of CagA+ multiple (≥ 2) EPIYA-C repeats showed that only the HLA-DQB1*06 allele [odds ratio (OR): 0.37, P = 0.036] was significantly lower, but significance was lost after correction (Pc = 0.1845). The HLA-DQA1*01 allele had a high ratio in GC cases with multiple EPIYA-C repeats, but this was not significant in the univariate analysis. We compared allele frequencies in the DU cases alone and in GC and DU cases together using the same criterion, and none of the HLA alleles were significantly associated with GC or DU. Also, none of the alleles were detected as independent risk factors after the multivariate analysis. On the other hand, in a multivariate logistic regression with no discriminative criterion, HLA-DQA1*01 (OR = 1.848), HLA-DQB1*06 (OR = 1.821) and HLA-A*02 (OR = 1.579) alleles were detected as independent risk factors for GC and DU. CONCLUSION None of the HLA alleles were detected as independent risk factors in terms of CagA+ multiple EPIYA-C repeats. However, HLA-DQA1*01, HLA-DQB1*0601, and HLA-A*2 were independent risk factors with no criterion in the multivariate analysis. We suggest that the association of these alleles with gastric malignancies is not specifically related to cagA and multiple EPIYA C repeats.

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Section: Discussionmentioning

confidence: 99%

Association between human leukocyte antigen gene polymorphisms and multiple EPIYA-C repeats in gastrointestinal disorders

Sarıbaş

Demiryas

Yılmaz

et al. 2020

WJG

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“…These results are on the contrary of those obtained in some studies. El Khadir noted a difference in the vacA and cagA combination of H. pylori in PUD and gastric cancer cases [20] [40]. Lehours did not find a difference between gastritis and gastric MALT lymphoma patients regarding H. pylori Open Journal of Medical Microbiology pathogenicity factors [20].…”

Section: Discussionmentioning

confidence: 93%

cagA and vacA Helicobacter pylori Pathogenicity Factors in Brazzaville, Congo

Ngoyi¹,

Guilloteau²,

Bénéjat³

et al. 2019

OJMM

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Introduction: CagA and VacA are the most important and well-studied virulence factors found in Helicobacter pylori. The aim of this work was to identify genes corresponding to H. pylori pathogenicity factors in Brazzaville, Congo. Material & Methods: A cross-sectional study was carried out from October 2013 to December 2016. Biopsy specimens were obtained from patients scheduled for upper gastrointestinal endoscopy in Brazzaville, Congo and were sent to the French National Reference Center for Campylobacters and Helicobacters in Bordeaux, France. H. pylori detection was conducted by real-time PCR using a fluorescence resonance energy transfer-melting curve analysis protocol. The identification of the genes encoding pathogenicity factors was carried out by conventional PCR using the appropriate primers for determination of CagA phosphorylation motifs 1, 2, 3; and vacAs, I and m regions: vacAi1, vacAi2, vacAs1a, vacAs1b. Results: A high prevalence of H. pylori infection was reported (108/143; 75.5%). In 92.2% (n = 71/77), the presence of P1, P2 and P3 CagA phosphorylation motifs was noted. Concerning vacA, vacAs1m1 was observed in 82% of the strains (n = 59/72). Va-cai1 was present in all strains (n = 76). With regard to the distribution according to the vacAs1 subtype, the majority of the strains (59/71; 83%) were vacAs1b positive, as compared to vacAs1c (17/34, 33%). The vacAs1a gene was absent in all of these patients. Conclusion: The presence of genes associated with severe gastric diseases indicates the importance of H. pylori eradication in the prevention of these diseases in Congo.

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“…The biopsies of these patients were previously used to characterize vacA-s, vacA-m, vacA-i regions and cagA 3 0 region polymorphism. 10,11 Therefore, in the present study, the correlation between vacA and cagA genotypes with histological lesions was established. Thus, all consenting patients had a personal interview before endoscopy, and were asked about individual characteristics.…”

Section: Patients and Samplingmentioning

confidence: 94%

“…For cagA positives samples, the 3 0 variable region of cagA encoding the EPIYA segments was analyzed using a combination of two approaches as previously described by our team. 11 The first one serves to determine the entire 3 0 -repeat region of cagA using the primers "Cag-TF/Cag-TR" which amplify a 350 to 400, 500, 600 and 700 bp fragments corresponding to (EPIYA-AB, EPIYA-BC or EPIYA-AC), EPIYA-ABC, EPIYA-ABCC and EPIYA-ABCCC, respectively. 16 The second approaches serve to determine each EPIYA-repeat segment independently (the amplification with primers cag2 and cagA-P1C identifies the EPIYA-A motif; amplification with primers cag2 and a 1:1 mixture of primers cagA-P2TA and cagA-P2GC identifies the EPIYA-B motif, while, the use of cag2 and cagA-P3E primers amplifies either EPIYA-C and EPIYA-D motifs, so to discriminate between those motifs, an additional reaction with cag2 and cagA-pD primer indicates EPIYA-D).…”

Section: Molecular Analysis Of H Pylorimentioning

confidence: 99%

“…The PCR products of the 3 0 cagA variable region of 16 and the data were processed with the Sequencing Analysis 3.3 software (Applied Biosystems, San Jose, California). The characterization of the C-terminal region of CagA was performed by analyzing the aminoacid sequences (using the site: http://web.expasy.org/translate/) to determine the type and number of EPIYA motifs as previously described by Panayotopoulou and coll.. 18 The obtained amino acid sequences were aligned with a partial CagA protein sequence from the H. pylori strain was published in our previous paper 11 and it is also reported in Figure S1, it confirm the perfect match between the PCR and sequencing results.…”

Section: Molecular Analysis Of H Pylorimentioning

confidence: 99%

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VacA genotypes and cagA‐EPIYA‐C motifs of Helicobacter pylori and gastric histopathological lesions

Khadir

Alaoui

Benajah

et al. 2020

Intl Journal of Cancer

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Helicobacter pylori infection induces inflammation of the gastric mucosa, which may progress to precancerous lesions and gastric cancer. The gastric histo-pathological damages may be associated with some virulence genes of the bacterium, notably vacA and cagA genes. To establish correlations between these genes and the lesions, biopsies from 1303 adults consenting patients that were previously analyzed by PCR to characterize vacA-s vacA-m, vacA-i regions and cagA 3 0 region polymorphism, were used. The highest average age was obtained in patients with intestinal metaplasia (53.65 ± 15.26 years) and gastric cancer (53.60 ± 14.32 years). Thus, these lesions are more frequent in elderly and male subjects. Tobacco smoking was significantly associated with neutrophilic activity (P = .02). No significant association was obtained between patients with chronic inflammation and vacA and cagA H. pylori genotypes. However, a significant association has been obtained between this lesion and cagA+ in aged patients (P = .02), while intestinal metaplasia was significantly associated with vacAi1 and vacAm1 separately (P < .01 and .01). Also, a significant association was obtained between intestinal metaplasia and strains with one EPIYA-C motif in young patients (P = .001). Interestingly, a significant association was obtained between gastric cancer and cagA+, vacAi1, vacAm1 H. pylori genotypes and also with two EPIYA-C motifs independently of age groups (all P < .05). The results of our study show that H. pylori vacAi1 could be more potent than the other H. pylori virulent factors for predicting the precancerous gastric lesions, confirming that this gene may be helpful to identify patients at high risk for gastric cancer.

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Helicobacter pylori CagA EPIYA-C motifs and gastric diseases in Moroccan patients

Cited by 19 publications

References 48 publications

Association between human leukocyte antigen gene polymorphisms and multiple EPIYA-C repeats in gastrointestinal disorders

Association between human leukocyte antigen gene polymorphisms and multiple EPIYA-C repeats in gastrointestinal disorders

<i>cagA</i> and <i>vacA</i> <i>Helicobacter pylori</i> Pathogenicity Factors in Brazzaville, Congo

VacA genotypes and cagA‐EPIYA‐C motifs of Helicobacter pylori and gastric histopathological lesions

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Helicobacter pylori CagA EPIYA-C motifs and gastric diseases in Moroccan patients

Cited by 19 publications

References 48 publications

Association between human leukocyte antigen gene polymorphisms and multiple EPIYA-C repeats in gastrointestinal disorders

Association between human leukocyte antigen gene polymorphisms and multiple EPIYA-C repeats in gastrointestinal disorders

&lt;i&gt;cagA&lt;/i&gt; and &lt;i&gt;vacA&lt;/i&gt; &lt;i&gt;Helicobacter pylori&lt;/i&gt; Pathogenicity Factors in Brazzaville, Congo

VacA genotypes and cagA‐EPIYA‐C motifs of Helicobacter pylori and gastric histopathological lesions

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<i>cagA</i> and <i>vacA</i> <i>Helicobacter pylori</i> Pathogenicity Factors in Brazzaville, Congo