scholarly journals vacA genotypes and EPIYA motifs of Helicobacter pylori in patients with atrophic and non-atrophic gastritis

2019 ◽  
Author(s):  
Santiago Escalante ◽  
Cesar Navarrete ◽  
Daniela Nuñez ◽  
Jorge Reyes ◽  
Andres Zabala ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Atrophic Gastritis ◽  
Precancerous Lesions ◽  
Molecular Techniques ◽  
Gastric Injury ◽  
Upper Gastrointestinal Endoscopy ◽  
Caga Gene ◽  
Vaca Gene ◽  
H Pylori ◽  
Epiya Motifs

Abstract Summary Background Helicobacter pylori is the main microorganism causing gastrointestinal diseases, such as chronic gastritis, peptic ulcer, MALT lymphoma, among others. The presence of the s1/m1 genotype of the vacA gene and EPIYA phosphorylation motifs of the cagA gene have been linked to the production of prolonged gastric inflammation. This study determines the presence of these virulence genotypes and their relationship with atrophic gastritis. Methods We included 231 patients with a history of dyspepsia undergoing upper gastrointestinal endoscopy. Samples of gastric tissue were taken to establish, through molecular techniques, the presence of H. pylori by amplifying the ureA and flaA2 housekeeping genes; in addition, the alleles of signal (s) and of the middle region (m) present in the vacA gene were amplified; and by sequencing the repeating patterns of the tyrosine phosphorylation motifs within the Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs of the cagA gene were also amplified. A chi-square test was performed in order to establish the relationship between the virulence genes and the degrees of gastric injury. Results A total of (91/231) samples were positive for H. pylori, of which (57/91) amplified the cagA gene and (66/91) the vacA gene. 81.8% (54/66) of the positive samples for the vacA gene showed the combination of the s1/m1 alleles, associated mostly with atrophic gastritis (AG). The most frequent EPIYA motifs were ABC and ABCC, with 54.4% (31/57) and 40.4% (23/57) respectively. A relation of the genes with AG and its injury severity with a p>0.05 value was observed. The cagA +/vacA s1/m1+/EPIYA ABC pattern is found in most samples. A p=0.02 relationship was found between the presence of the vacA gene and the cagA gene. Conclusions The results show a higher proportion of gastric atrophy in patients infected with H. pylori. The sum of the pathogenicity factors such as the cagA+/vacA s1/m1+/EPIYA ABCC genotype increases the virulence potential of the microorganism, suggesting that the coexistence of these genes could result in an increase in the severity of the progression of inflammation that leads to precancerous lesions.

scholarly journals Eradication of Helicobacter pylori and Gastric Cancer: A Controversial Relationship

2021 ◽  
Vol 12 ◽  
Author(s):  
Mariagrazia Piscione ◽  
Mariangela Mazzone ◽  
Maria Carmela Di Marcantonio ◽  
Raffaella Muraro ◽  
Gabriella Mincione
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Atrophic Gastritis ◽  
Precancerous Lesions ◽  
Eradication Therapy ◽  
Developed Countries ◽  
Gastric Carcinogenesis ◽  
Gastric Disease ◽  
Type I ◽  
H Pylori

Worldwide, gastric cancer (GC) represents the fifth cancer for incidence, and the third as cause of death in developed countries. Indeed, it resulted in more than 780,000 deaths in 2018. Helicobacter pylori appears to be responsible for the majority of these cancers. On the basis of recent studies, and either alone or combined with additional etiological factors, H. pylori is considered a “type I carcinogen.” Over recent decades, new insights have been obtained into the strategies that have been adopted by H. pylori to survive the acidic conditions of the gastric environment, and to result in persistent infection, and dysregulation of host functions. The multistep processes involved in the development of GC are initiated by transition of the mucosa into chronic non-atrophic gastritis, which is primarily triggered by infection with H. pylori. This gastritis then progresses into atrophic gastritis and intestinal metaplasia, and then to dysplasia, and following Correa’s cascade, to adenocarcinoma. The use of antibiotics for eradication of H. pylori can reduce the incidence of precancerous lesions only in the early stages of gastric carcinogenesis. Here, we first survey the etiology and risk factors of GC, and then we analyze the mechanisms underlying tumorigenesis induced by H. pylori, focusing attention on virulence factor CagA, inflammation, oxidative stress, and ErbB2 receptor tyrosine kinase. Moreover, we investigate the relationships between H. pylori eradication therapy and other diseases, considering not only cardia (upper stomach) cancers and Barrett’s esophagus, but also asthma and allergies, through discussion of the “hygiene hypothesis. ” This hypothesis suggests that improved hygiene and antibiotic use in early life reduces microbial exposure, such that the immune response does not become primed, and individuals are not protected against atopic disorders, asthma, and autoimmune diseases. Finally, we overview recent advances to uncover the complex interplay between H. pylori and the gut microbiota during gastric carcinogenesis, as characterized by reduced bacterial diversity and increased microbial dysbiosis. Indeed, it is of particular importance to identify the bacterial taxa of the stomach that might predict the outcome of gastric disease through the stages of Correa’s cascade, to improve prevention and therapy of gastric carcinoma.

DETERMINATION OF HELICOBACTER PYLORI CAGA GENE AND VACA GENOTYPES IN PATIENTS WITH GASTRIC CANCER

2013 ◽  
pp. 118-125
Author(s):  
Quy Hung Le ◽  
Thi Minh Thi Ha
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Signet Ring Cell ◽  
Tubular Adenocarcinoma ◽  
Negative Group ◽  
Caga Gene ◽  
Positive Group ◽  
Histopathological Classification ◽  
Vaca Gene ◽  
H Pylori

Background: H. pylori is the first cause of gastric cancer (GC). However, the role of cagA gene and vacA gene in GC is still controversial. This study is aimed at determining the rates of H. pylori infection, cagA gene, vacA genotypes in patients with GC; and evaluating the relationship between cagA gene, vacA genotypes and endoscopic and histopathological features of gastric cancer. Patients and methods: Fifty eight GC patients and one hundred and sixteen non-GC patients (controls) were enrolled. Infection of H. pylori was determined by PCR. cagA gene and vacA genotypes were determined by Multiplex PCR. Results: The rate of H. pylori was found in 55.2% in GC group. The rate of cagA gene and vacA gene in GC patients H. pylori positive were found in 78.1% and 100%, respectively. vac A genotypes s1/m1, s1/m2 and s1/m1m2 were found in 34.4%; 50% and 15.6%, respectively. The risk of GC of cagA positive group was higher than cagA negative group, with OR = 4,5; 95%CI = 1.6-12.2. The risk of GC of vacA s1/m1, cagA positive group was higher than vacA s1/m1, cagA negative group, OR = 7.1; 95%CI = 1.4-36. A statistically significative difference of rate of cagA positive was found between Borrmann III/IV group (100%) and Borrmann I/II group (46.2%). A statistically significative difference of rate of cagA positive was found between the tubular adenocarcinoma group (100%) and signet-ring cell carcinoma (44.4%, p = 0,002), and mucinous adenocarcinoma (50%, p =0,024). Conclusion: Gene cagA and vacA s1/m1 genotype were both risk factors in GC. A significative differences of rate of cagA positive were found between Borrmann groups, and between groups of WHO histopathological classification. Key words: cagA gene and vacA genotype, Helicobacter pylori, gastric cancer

scholarly journals Review of Research on Routes of Helicobacter pylori Infection

2015 ◽  
Vol 4 (2) ◽  
pp. 45-49
Author(s):  
Hang Li
Keyword(s):  
Helicobacter Pylori ◽  
Drinking Water ◽  
Peptic Ulcer ◽  
Gastric Mucosa ◽  
Atrophic Gastritis ◽  
Intestinal Metaplasia ◽  
Gastric Adenocarcinoma ◽  
Precancerous Lesions ◽  
Natural Environments ◽  
H Pylori

AbstractIn recent years, many scholars conducted in-depth research onHelicobacter pyloriand identified it as an important pathogen of chronic gastritis and peptic ulcer.H. pylorialso causes also and contributes to precancerous lesions (atrophic gastritis and intestinal metaplasia) and is closely related to occurrence and development of gastric adenocarcinoma and gastric mucosa-associated lymphoma. This study summarizes biological characteristics, epidemic status, and infection route ofH. pyloriand reviews research on roles of natural environments, especially drinking water, during infection.

scholarly journals Significance of Helicobacter pylori Eradication on Atrophic Gastritis and Intestinal Metaplasia

2020 ◽  
Vol 20 (2) ◽  
pp. 107-116
Author(s):  
Kichul Yoon ◽  
Nayoung Kim
Keyword(s):  
Helicobacter Pylori ◽  
Atrophic Gastritis ◽  
Intestinal Metaplasia ◽  
Precancerous Lesions ◽  
Eradication Therapy ◽  
Diffuse Type ◽  
Helicobacter Pylori Eradication ◽  
Predicting Factors ◽  
Point Of No Return ◽  
H Pylori

There has been an accumulation of data regarding the chemopreventive effects of <i>Helicobacter pylori</i> (<i>H. pylori</i>) eradication. However, it remains unclear how <i>H. pylori</i> infection causes gastric cancer (GC) and how <i>H. pylori</i> eradication can prevent GC. Atrophic gastritis (AG) and intestinal metaplasia (IM) are known as precancerous lesions which mainly lead to intestinal-type GC but to some extent, can also lead to diffuse-type GC. The most important mechanism of AG/IM is <i>H. pylori</i>-induced chronic gastritis. Thus, the reversibility of AG and IM by <i>H. pylori</i> eradication therapy is very important in the prevention of GC. There have been many studies providing data supporting the improvement of AG by the eradication of <i>H. pylori</i> to some extent. In contrast, IM has been regarded as “the point of no return.” However, more recent studies have implied the improvement of IM after eradication, suggesting the importance of early eradication therapy in reversible histological status. In this review, we focused on the reversibility of AG and IM by <i>H. pylori</i> eradication and tried to investigate the predicting factors for the improvement of AG and IM including age, sex, smoking, and diet, as well as <i>H. pylori</i> infection.

scholarly journals Association of Helicobacter pylori vacA polymorphisms with the risk of gastric precancerous lesions in a Moroccan population

2021 ◽  
Vol 15 (08) ◽  
pp. 1124-1132
Author(s):  
Mohamed Reda Jouimyi ◽  
Ghizlane Bounder ◽  
Imane Essaidi ◽  
Hasna Boura ◽  
Wafaa Badre ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
High Risk ◽  
Atrophic Gastritis ◽  
Intestinal Metaplasia ◽  
Chronic Gastritis ◽  
Precancerous Lesions ◽  
Gastric Lesions ◽  
D Region ◽  
Reliable Marker ◽  
H Pylori

Introduction: Helicobacter pylori infection is the major risk factor of atrophic gastritis and intestinal metaplasia. The vacA gene is one of the most virulence factors of H. pylori and genetic diversity in its s, m, i, and d regions is associated with gastric lesions severity. This study aimed to investigate the association of vacA s, m, i, and d regions with the risk of atrophic gastritis and intestinal metaplasia in a Casablanca population. Methodology: A total of 210 patients suffering from gastric lesions (chronic gastritis, atrophic gastritis, and intestinal metaplasia) were enrolled. The type of lesion was diagnosed by histological examination. Detection of H. pylori infection and genotyping of vacA regions were carried out by PCR. Results: The prevalence of H. pylori was 95%. The most common vacA genotypes were s2 (51.5%), m2 (77%), i2 (60.5%), and d2 (58.5%). VacA s1, m1, and i1 genotypes were associated with a high risk of intestinal metaplasia, while the vacA d1 genotype increases the risk of atrophic gastritis and intestinal metaplasia. The most common vacA combination was s2/m2/i2/d2 (52%), and it was more detected in chronic gastritis. The moderate virulent vacA combination (s1/m2/i1/d1) increases the risk of atrophic gastritis, while the most virulent vacA combination (s1/m1/i1/d1) increases the risk of intestinal metaplasia. Conclusions: Genotyping of vacA d region might be a reliable marker for the identification of vacA virulent strains that represent a high risk of developing precancerous lesions (atrophic gastritis and intestinal metaplasia).

scholarly journals Helicobacter pylori cagA gene Polymorphism in Patients with Gastroduodenal Diseases

2018 ◽  
Vol 43 (1) ◽  
pp. 37-43
Author(s):  
Mahbuba Chowdhury ◽  
Sharmeen Ahmed ◽  
A.F.M.A.L Masum Khan ◽  
Shirin Tarafdar ◽  
Ruhul Amin Miah
Keyword(s):  
Duodenal Ulcer ◽  
Helicobacter Pylori ◽  
Gastric Ulcer ◽  
Gastric Carcinoma ◽  
Peptide Sequence ◽  
Rapid Urease Test ◽  
Caga Gene ◽  
Urease Test ◽  
H Pylori ◽  
Epiya Motifs

Helicobacter pylori is a genetically diverse bacterial pathogen and its CagA gene is a major virulence factor that plays an important role in gastroduodenal pathologies. The biological function of cagA depends on tyrosine phosphorylation within the EPIYA (Glutamate-Proline-Isoleucine-Tyrosine-Alanine) motifs at the C-terminal region of the protein. This region may undergo polymorphism to give different types of EPIYA motifs. EPIYA motif diversity may provide a useful tool for prediction of H. pylori pathogenic activity and accurate determination of number and type of cagA EPIYA motifs could identify the virulent H. pylori. The aim of this study was to detect H. pylori cagA gene and its polymorphism in endoscopic gastroduodenal biopsy specimen from patients with gastroduodenal diseases in Bangladesh. This cross sectional study was carried out in the Department of Microbiology & Immunology, Bangabandhu Sheikh Mujib Medical University and Center for Advanced Research in Sciences, University of Dhaka during the period from March 2014 to February 2015. Gastric biopsies were collected from 78 patients with gastritis, duodenal ulcer, gastric ulcer and gastric carcinoma. H. pylori was identified by rapid urease test and ureC gene PCR. Presence of cagA gene and number and pattern of cagA EPIYA motif were determined by PCR. DNA sequencing was carried out to confirm the PCR detection method of cagA EPIYA motif and to analyse their peptide sequence. Among 31(39.7%) H. pylori positive cases, 19 (61.3%) were cagA gene positive in 11(55%) gastritis, 4(66.7%) duodenal ulcer, 2(66.7%) gastric ulcer and 2(100%) gastric carcinoma. A significant association was found between cagA gene and duodenal ulcer (p=˂0.05). EPIYA motif of all H. pylori cagA positive cases showed Western type cagA EPIYA ABC. No East Asian EPIYA ABD motif was found. Majority of gastroduodenal cases (57.9%) had 3 copies of EPIYA (ABC type), 26.3% had 4 copies (ABCC type) while remaining 10.5% had AC and 5.2% AB type EPIYA motif. EPIYA ABC was found in 75% of duodenal ulcer followed by 54.5% of gastritis and 50% of both gastric ulcer and gastric carcinoma patients. EPIYA ABCC motif was found in 50% of gastric ulcer and gastric carcinoma patients. Most of the EPIYA motif was EPIYA ABC and some were ABCC which has the risk of developing gastric carcinoma.

scholarly journals Evaluation of the Pattern of EPIYA Motifs in the Helicobacter pylori cagA Gene of Patients with Gastritis and Gastric Adenocarcinoma from the Brazilian Amazon Region

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Adenielson Vilar e Silva ◽  
Mario Ribeiro da Silva Junior ◽  
Ruth Maria Dias Ferreira Vinagre ◽  
Kemper Nunes Santos ◽  
Renata Aparecida Andrade da Costa ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Intestinal Metaplasia ◽  
Gastric Adenocarcinoma ◽  
Brazilian Amazon ◽  
Caga Gene ◽  
Neutrophil Activity ◽  
Increased Risk ◽  
Brazilian Amazon Region ◽  
H Pylori ◽  
Epiya Motifs

The Helicobacter pylori is associated with the development of different diseases. The clinical outcome of infection may be associated with the cagA bacterial genotype. The aim of this study was to determine the EPIYA patterns of strains isolated from patients with gastritis and gastric adenocarcinoma and correlate these patterns with the histopathological features. Gastric biopsy samples were selected from 384 patients infected with H. pylori, including 194 with chronic gastritis and 190 with gastric adenocarcinoma. The presence of the cagA gene and the EPIYA motif was determined by PCR. The cagA gene was more prevalent in patients with gastric cancer and was associated with a higher degree of inflammation, neutrophil activity, and development of intestinal metaplasia. The number of EPIYA-C repeats showed a significant association with an increased risk of gastric carcinoma (OR = 3.79, 95% CI = 1.92–7.46, and P=0.002). A larger number of EPIYA-C motifs were also associated with intestinal metaplasia. In the present study, infection with H. pylori strains harboring more than one EPIYA-C motif in the cagA gene was associated with the development of intestinal metaplasia and gastric adenocarcinoma but not with neutrophil activity or degree of inflammation.

scholarly journals The association of Helicobacter pylori CagA EPIYA motifs and vacA genotypes with homologous recombination repair markers during the gastric precancerous cascade

2020 ◽  
Vol 35 (2) ◽  
pp. 49-55
Author(s):  
Yang Mi ◽  
Haibin Dong ◽  
Xiangdong Sun ◽  
Feifei Ren ◽  
Youcai Tang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Helicobacter Pylori ◽  
Homologous Recombination ◽  
Molecular Mechanisms ◽  
Precancerous Lesions ◽  
Homologous Recombination Repair ◽  
Recombination Repair ◽  
H Pylori ◽  
Epiya Motifs ◽  
Damage Marker

Background: Helicobacter pylori-induced DNA damage and impaired homologous recombination repair are vital molecular mechanisms for gastric cancer, which mainly count on its virulence factors cytotoxic-associated gene A (CagA) and vacuolating cytotoxin A (VacA). However, the relationship between H. pylori CagA EPIYA motifs and vacA genotypes with DNA damage and homologous recombination repair markers is still not clear. Methods: H. pylori positive and negative gastric biopsies were taken from 165 subjects with different gastric precancerous pathologic stages, and DNA damage marker γH2AX and key homologous recombination repair proteins (CtIP and Rad51) were investigated for their association with H. pylori CagA EPIYA motifs and vacAs-, m-, i-, and d-region genotypes and histology (Sydney classification). Results: Out of 165 patients, 78 were identified as H. pylori-positive. CagA EPIYA motifs were identified as AB, ABC, and ABD in 2 (3.3%), 21 (35%), and 37 (61.7%) patients, respectively, while vacA alleles were identified as: s1, s2, m1, m2, i1, i2, d1, and d2 in 50 (89.3%), 6 (10.7%), 24 (42.9%), 32 (57.1%), 45 (80.4%), 11 (19.6%), 40 (71.4%), and 16 (28.6%) patients, respectively. vacAs1m1i1d1, s1m2i1d1, and s1m2i2d2 were the most prevailing genotypes. γH2AX was highly localized in H. pylori-positive tissues with corresponding CagA EPIYA motifs and vacA genotypes, while Rad51 and CtIP signals were weak. Conclusion: H. pylori were positively correlated with the DNA damage marker in precancerous lesions, but were negatively correlated with the key homologous recombination repair proteins, which may be due to the specific CagA EPIYA motifs and vacA genotypes.

scholarly journals A DNA Sequence Analysis of Helicobacter pylori in Jeddah City, Western Saudi Arabia

2020 ◽  
Vol 11 (2) ◽  
pp. 2758-2764
Author(s):  
Abrar A. M. Almehmadi ◽  
Faten A. S. Alsulaimany
Keyword(s):  
Helicobacter Pylori ◽  
Saudi Arabia ◽  
Sequence Analysis ◽  
Virulence Factors ◽  
Dna Sequences ◽  
Sequencing Analysis ◽  
Caga Gene ◽  
Jeddah City ◽  
Vaca Gene ◽  
H Pylori

Helicobacter pylori are the type of Gram-negative bacteria which colonize the mucous lining of the human stomach. These bacteria have two major virulence factors: (vacuolating cytotoxin A gene) and (cytotoxin-associated A gene). This study aimed to provide data to determine the prevalent virulence factors (vacA and cagA genes) in Jeddah city, western Saudi Arabia, by sequence analysis. This study included 60 patients with symptoms similar to H. pylori infection. H. pylori were identified by using the 16s rRNA sequence. Then, the screening for specific genes in H. pylori (vacA and cagA) was done by using automated DNA sequencing analysis, and the DNA sequences were compared by BLAST and sequence alignment of the vacA nucleotides that are present in all H. pylori strains using those already reported in GeneBank from various studies. Results indicated that H. pylori infection was detected in 13.3%, while 86.7% were negative samples in our study patients. Interestingly, the vacA gene was found in 8.3%, while the cagA gene was not appear in patient. Also, the female prevalence rate was higher than males (11.7% female versus 1.7% males), and the highest infection was between age 40-49 by 6.7%. In conclusion, this study revealed that the vacA gene was spread in the patients infected with H. pylori in Jeddah, while the cagA gene was not appear in any isolate.

scholarly journals Serodiagnosis and Bacterial Genome of Helicobacter pylori Infection

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 467
Author(s):  
Aina Ichihara ◽  
Hinako Ojima ◽  
Kazuyoshi Gotoh ◽  
Osamu Matsushita ◽  
Susumu Take ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibody Titer ◽  
Bacterial Genome ◽  
Serum Antibody ◽  
Gene Mutations ◽  
Bacterial Genomes ◽  
Western Blots ◽  
A Genome ◽  
Vaca Gene ◽  
H Pylori

The infection caused by Helicobacter pylori is associated with several diseases, including gastric cancer. Several methods for the diagnosis of H. pylori infection exist, including endoscopy, the urea breath test, and the fecal antigen test, which is the serum antibody titer test that is often used since it is a simple and highly sensitive test. In this context, this study aims to find the association between different antibody reactivities and the organization of bacterial genomes. Next-generation sequences were performed to determine the genome sequences of four strains of antigens with different reactivity. The search was performed on the common genes, with the homology analysis conducted using a genome ring and dot plot analysis. The two antigens of the highly reactive strains showed a high gene homology, and Western blots for CagA and VacA also showed high expression levels of proteins. In the poorly responsive antigen strains, it was found that the inversion occurred around the vacA gene in the genome. The structure of bacterial genomes might contribute to the poor reactivity exhibited by the antibodies of patients. In the future, an accurate serodiagnosis could be performed by using a strain with few gene mutations of the antigen used for the antibody titer test of H. pylori.

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