Determination of Helicobacter pylori virulence by analysis of the cag pathogenicity island isolated from Iranian patients (original) (raw)
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Clinical and Vaccine Immunology, 2001
Nucleic acid amplification was performed for five loci in thecag pathogenicity island (PAI) of Helicobacter pylori (comprising cagA, the cagApromoter region, cagE, cagT, and the left end of cagII [LEC]), and gastric inflammation in patients was evaluated. Of 204 H. pylori isolates from Japanese patients (53 with peptic ulcer, 55 with gastric cancer, and 96 with chronic gastritis), 197 (96.6%) were positive for all five loci. Two isolates (1%) were negative for all five loci, and five isolates (2.4%) were positive for only cagA and LEC. These latter seven isolates were all from patients with mild chronic gastritis. Neutrophil infiltration in gastric mucosa was significantly milder in patients infected with partially or totally deleted-PAI strains than in those with intact-PAI strains. The cagE gene was a more accurate marker of an intact cag PAI than thecagA gene, and cagE seemed to be more useful in discriminating between H. pylori strains causing different rates of disease progress...
World Journal of Microbiology and Biotechnology, 2014
Helicobacter pylori infection is common in Iran as in other developing countries. Certain genotypes of H. pylori have been associated with increased occurrence of chronic gastritis, peptic ulcers, and gastric adenocarcinoma. The aim of this study was to investigate the clinical relevance of cagL gene and other virulence genotypes of H. pylori isolates with clinical outcomes in Iranian patients. Totally, 126 symptomatic patients who underwent gastroduodenal endoscopy were enrolled in the study. Sixty-one H. pylori strains were isolated from the patients studied. The presence of the cagL, cagA, vacA, iceA, babA2 and sabA genes in the corresponding H. pylori isolates were determined by polymerase chain reaction and the results were compared with clinical outcomes and histopathology. The cagL, cagA, vacA s1, vacA s2, vacA m1, vacA m2, iceA1, iceA2, babA 2 , and sabA genotypes were detected in 96.7, 85.2, 75.4, 24.6, 29.5, 70.5, 42.6, 23, 96.7, and 83.6 % of the isolates, respectively. The three genotypic combinations, cagL/cagA/vacAs1m1/iceA1/babA2/sabA, cagL/cagA/vacAs1m2/iceA1/babA2/sabA, and cagL/cagA/ vacAs1m2/iceA2/babA2/sabA were determined as the most prevalent combined genotypes. There was a significant correlation between the presence of cagL gene and cagA positivity (P = 0.02). No significant correlation was found between the various genotypes and clinical outcomes (P [ 0.05). The present study showed a very high prevalence of cagL genotype among the H. pylori isolates from Iranian patients. Our results demonstrated that neither single genotype nor combination genotypes of virulenceassociated genes was significantly helpful markers for predicting the severity of gastroduodenal disease associated with H. pylori infection in Iranian patients.
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2018
One of the most important virulence factors of H. pylori is the intact cagPAI. The aim of the present study is to investigate cagPAI intactness among Bulgarian H. pylori isolates, its associations with clinical outcomes and vacA alleles, and to evaluate the significance of individual cagPAI genes. Totally, 156 isolates from 156 patients with endoscopic findings for duodenal or gastric ulcer (33 subjects), non-ulcer disease (121) and other diseases, such as Crohn's disease and hepatitis (2) were tested. Polymerase chain reaction (PCR) was used to detect 14 essential cagPAI genes, including cagA, as well as vacA s, i and m alleles. CagA positive were 81.4% of all H. pylori isolates. Intact cagPAI was found in 64.1% of the all isolates, 16.7% and 19.2% showed complete and partial cagPAI absence, respectively. The prevalence of all cagPAI genes and intact cagPAI was significantly higher in isolates from ulcer patients compared with those from non-ulcer patients (p = 0.001). The most...
Background: There is an increase in the prevalence of Helicobacter pylori infection in Sudan, accompanied by a high incidence of upper gastrointestinal malignancy. The cytotoxin-associated gene cagA gene is a marker of a pathogenicity island (PAI) in H. pylori and plays a crucial role in determining the clinical outcome of Helicobacter infections. Objective: This study aimed to determine the frequency and heterogeneity of the cagA gene of H. pylori and correlate the presence of cagA gene with clinical outcomes. Materials and methods: Fifty endoscopy biopsies were collected from Fedail and Soba hospitals in Khartoum state. DNA was extracted using the Guanidine chloride method followed by PCR to amplify 16S rRNA and cagA gene of H. pylori using specific primers. DNA amplicons of cagA gene were purified and sequenced. Bioinformatics and statistical analysis were done to characterize and to test the association between cagA gene and gastric complications. Results: CagA gene was detected...
Prevalence and Diversity of Cag (PAI) in Helicobacter pylori: Study on Gastric Ulcer
Journal of Gastrointestinal & Digestive System, 2018
Background: Frequency of H. Pylori in northern part of Iran within normal population is about 90% which is high, particular marker in order to diagnose patients with higher risk of peptic ulcer disease progression would be helpful for clinical practice. The purpose of this study was to evaluate the variable locus of CagA gene in virulence form. Methods: For this aim 200 types of biopsy infected and positive urease test and 20 samples of healthy people biopsies in order for control were provided. After DNA purification, the variety of locus in CagA gene was confirmed by glmM, SSA and CagV primers. Results: The results showed that 142 typical were positive for CagA. CagV primer used to variety fixed. The CagV gene exposed a special genetic variety in the 800 bp, 825 bp, 850 bp, 900 bp areas. Conclusions: The result of study on this locus suggested that variation of CagV could be consider as a paradigm in intensity and distribution of the gastric ulcer disease and key marker to prevent progression or inhibition of the progress in gastrointestinal disease.
British Journal of Biomedical Science, 2009
Clinical diseases that follow Helicobacter pylori infection are associated with expression of the cagA gene, a part of cytotoxin-associated gene pathogenicity island (cag-PAI). This study aims to determined whether or not the presence of cagA is associated with the presence of complete cag-PAI and to evaluate inflammatory changes associated with the five loci in the cag-PAI of H. pylori comprising cagA, cagA promoter region (cagAP), cagE, cagT and the left end of the cagA gene (LEC). H. pylori isolates were obtained from patients with dyspeptic symptoms. Clinical strains of H. pylori were screened by the polymerase chain reaction (PCR) for respective genes of the cag-PAI. Of 115 H. pylori isolates, 31 (28%) were positive for the five cag-PAI loci. H. pylori isolates with intact cag-PAI were associated with gastric carcinoma (GC; n=9[60%]) and gastric ulcer (GU; n=5[45%]) compared to non-ulcer dyspepsia (NUD; n=14[18%]) (P=0.001 and P=0.049, respectively). In patients with intact cag-PAI, acute on chronic inflammation was present in 25 (81%) and was more common than chronic inflammation (P=0.013). The cagE and cagAP had deletions in 25 (37%) and 23 (35%) cases, respectively. The cagAP region was significantly associated with GC (n=12[80%], P<0.001) and GU (n=9[82%], P=0.001) compared to NUD (n=24[30%] and with significant acute on chronic inflammation (n=40[80%], P=0.007). The distribution of vacAs1a with intact cag-PAI in GC was 9(60%) and in NUD was 10(13%) (P<0.001). The presence of the cagA gene does not signify presence of an intact cag-PAI. Most of the H. pylori isolates studied had partial cag-PAI with missing cagE and cagA promoter regions.
Diagnostic Microbiology and Infectious Disease, 2007
Helicobacter pylori is a bacterium associated with upper gastrointestinal diseases in humans. However, only a small proportion of infected people become sick. Although several studies have tried to establish an association between known virulence markers and clinical outcomes, in many cases the results have been conflicting. The aim of this study was to investigate the importance of virulence markers to predict clinical outcome in Brazil. Mixed infections by genetically unrelated strains detected by vacA genotyping were found in 18% of the patients. The cagA and cagE genes and the vacAs1 genotype were associated with the development of peptic ulcer disease (PUD). The cagAvacAs1m1 genotype was associated with PUD and duodenal ulcer (DU). Conversely, jhp947 was not associated with DU or PUD, indicating that this gene is not a universal virulence marker. These results also show that a high proportion of the patients were simultaneously infected by cag-positive and cag-negative H. pylori types. This finding suggests the existence of a dynamic equilibrium between the loss and gain of the cag pathogenicity island, probably depending on the physiologic conditions of the patient's stomach. To the best of our knowledge, this is the first study that has documented this finding in Brazil.
Biomedical Research-tokyo, 2017
Objective(s): Helicobacter pylori are gastric infectious agents that colonizes majority of the world's population. Genetic diversity among the virulence factors of bacterium like cytotoxin associated gene Pathogenicity Island (cagPAI) and vacuolating cytotoxinA (vacA) could have a modifying result on the pathogenic potential of the infecting strain. This study aimed to analyse which genes can be recommended as doubtless related virulence factors for H. pylori associated active chronic gastritis and stomach adenocarcinoma in Iranian and Turkish population. Material and methods: We tend to targeted on some cag PAI components and vacA gene subtypes based on correlations shown in some previous studies. So as to realize our goal, formalin fixed Paraffin Embedded (FFPE) tissues obtained from Iranian and Turkish patients. The prevalence of the cagPAI and vacA genotypes were studied in H. pylori positive samples by using Polymerase Chain Reaction (PCR) technique and specific primers. Results: From all of 320 patients, H. pylori were detected in 28.43% of patients. We tend to found that vacAs1, vacAm2 and cagA genes with mean prevalence of 82.41%, 71.42% and 69.23% were dominant in both of Iranian and Turkish patients. Conclusion: Finally in Turkish and Iranian population the genes that were studied, was homogeneous and there's no important variations in bacterial genetic and with the exception of H. pylori infection different factors like host genetic and nourishment play a crucial role within the formation of gastric cancer. However it's attainable that if statistical population will increase, the cagA gene association with cancer are going to be meaningful.
Saudi Journal of Gastroenterology, 2013
Helicobacter pylori is a Gram-negative bacteria that inhabit the gastric mucosal lining. Adhesion of the bacteria to the gastric mucosa is a necessary prerequisite for the pathogenesis of H. pylori-related diseases. Although most patients are asymptomatic, persistent infection may cause chronic gastritis, gastric ulcer, gastric cancer, and duodenal ulcer. The prevalence varies among countries with existing evidence suggesting that the diversity in disease outcome may be ascribed to variations in infecting strains. [1,2] The virulence markers of H. pylori, such as cytotoxin-associated genes A (cagA) and E (cagE), vacuolating cytotoxin (vacA) and its alleles have been shown to be associated with its various manifestations. [3] H. pylori genotypes and their geographic distribution are linked to the severity of peptic ulcer disease (PUD). [4,5] The H. pylori genome is genetically diverse, as it can be seen in the cag pathogenicity island (PAI) and allelic variation within the vacA gene. [5,6] The cytotoxin-associated gene A (cagA) has been proposed as a marker for the cag PAI and is associated with more severe clinical outcomes. [3-5] The cag PAI genes contain a cagE gene that encodes a secretory protein that is required for the induction of interleukin-8 and for translocation and phosphorylation of CagA protein. [7,8] The cagE genotype has been associated with gastric cancer in ABSTRACT Background/Aim: Helicobacter pylori is a Gram-negative bacteria, which is associated with development of gastroduodenal diseases. The prevalence of H. pylori and the virulence markers cytotoxin-associated gene A and E (cagA, cagE) and vacuolating-associated cytotoxin gene (vacA) alleles varies in different parts of the world. H. pylori virulence markers cagA, cagE, and vacA alleles in local and Afghan nationals with H. pylori-associated gastroduodenal diseases were studied. Patients and Methods: Two hundred and ten patients with upper gastrointestinal symptoms and positive for H. pylori by the urease test and histology were included. One hundred and nineteen were local nationals and 91 were Afghans. The cagA, cagE, and vacA allelic status was determined by polymerase chain reaction. Results: The nonulcer dyspepsia (NUD) was common in the Afghan patients (P = 0.025). In Afghan H. pylori strains, cagA was positive in 14 (82%) with gastric carcinoma (GC) compared with 29 (45%) with NUD (P = 0.006), whereas cagE was positive in 11 (65%) with GC and 4 (67%) with duodenal ulcer (DU) compared with 12 (18%) with NUD (P < 0.001 and 0.021, respectively). The vacA s1a/b1was positive in 10 (59%) of GC compared with 20 (31%) in NUD (P = 0.033). In Pakistani strains, cagE was positive in 12 (60%) with GC, 7 (58%) with GU, 12 (60%) with DU compared with 11 (16%) with NUD (P < 0.001, 0.004, and < 0.001, respectively). In Pakistani strains, cagA/s1a/m1 was 39 (33%) compared with Afghans in 17 (19%) (P = 0.022). Moderate to severe mucosal inflammation was present in 51 (43%) Pakistani patients compared with 26 (28%) (P = 0.033) in Afghans. It was also associated with grade 1 lymphoid aggregate development in Pakistani patients 67 (56%) compared with 36 (40%) (P = 0.016) in Afghans. Conclusion: Distribution of H. pylori virulence marker cagE with DU was similar in Afghan and Pakistan H. pylori strains. Chronic active inflammation was significantly associated with Pakistani H. pylori strains.