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Soyfoo DM, Doomah YH, Xu D, Zhang C, Sang HM, Liu YY, Zhang GX, Jiang JX, Xu SF. New genotypes of Helicobacter Pylori VacA d-region identified from global strains. BMC Mol Cell Biol 2021; 22:4. [PMID: 33413074 PMCID: PMC7791883 DOI: 10.1186/s12860-020-00338-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 12/16/2020] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Pathogenesis of Helicobacter Pylori (HP) vacuolating toxin A (vacA) depends on polymorphic diversity within the signal (s), middle (m), intermediate (i), deletion (d) and c-regions. These regions show distinct allelic diversity. The s-region, m-region and the c-region (a 15 bp deletion at the 3'-end region of the p55 domain of the vacA gene) exist as 2 types (s1, s2, m1, m2, c1 and c2), while the i-region has 3 allelic types (i1, i2 and i3). The locus of d-region of the vacA gene has also been classified into 2 genotypes, namely d1 and d2. We investigated the "d-region"/"loop region" through bioinformatics, to predict its properties and relation to disease. One thousand two hundred fifty-nine strains from the NCBI nucleotide database and the dryad database with complete vacA sequences were included in the study. The sequences were aligned using BioEdit and analyzed using Lasergene and BLAST. The secondary structure and physicochemical properties of the region were predicted using PredictProtein. RESULTS We identified 31 highly polymorphic genotypes in the "d-region", with a mean length of 34 amino acids (9 ~ 55 amino acids). We further classified the 31 genotypes into 3 main types, namely K-type (strains starting with the KDKP motif in the "d-region"), Q-type (strains starting with the KNQT motif), and E-type (strains starting with the ESKT motif) respectively. The most common type, K-type, is more prevalent in cancer patients (80.87%) and is associated with the s1i1m1c1 genotypes (P < .01). Incidentally, a new region expressing sequence diversity (2 aa deletion) at the C-terminus of the p55 domain of vacA was identified during bioinformatics analysis. CONCLUSIONS Prediction of secondary structures shows that the "d-region" adopts a loop conformation and is a disordered region.
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Affiliation(s)
- Djaleel Muhammad Soyfoo
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yussriya Hanaa Doomah
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Dong Xu
- Department of Electrical Engineering and Computer Science, Bond Life Sciences Center, University of Missouri, Columbia, MO, USA
| | - Chao Zhang
- Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, 10021, USA.,Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY, 10021, USA
| | - Huai-Ming Sang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yan-Yan Liu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Guo-Xin Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jian-Xia Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
| | - Shun-Fu Xu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
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Kalan Farmanfarma K, Mahdavifar N, Hassanipour S, Salehiniya H. Epidemiologic Study of Gastric Cancer in Iran: A Systematic Review. Clin Exp Gastroenterol 2020; 13:511-542. [PMID: 33177859 PMCID: PMC7652066 DOI: 10.2147/ceg.s256627] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 09/14/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) is one of the most common cancers in Iran. Knowledge of the epidemiology of the disease is essential in planning for prevention. So this study aimed to investigate the epidemiological aspects of gastric cancer including prevalence, incidence, mortality, and risk factors of Iran. METHODS This systematic review study was based on articles published in both English and Persian languages during the years of 1970-2020 in international databases (PubMed, Web of Science, Scopus) and national databases (including SID, Magiran, and IranDoc). Papers related to epidemiological aspects of the disease including mortality, prevalence, incidence, and risk entered the final review. RESULTS According to the studies, the minimum and maximum prevalence of gastric cancer in northwestern Iran (Ardabil) is between 0.2 and 100 per 100,000. Also, the death rate per 100,000 people ranged from 10.6 to 15.72 and the ASMR ranged from 4.2 to 32.2%. On the other hand, the incidence of GC was higher in men than in women (74.9 vs 4.6%). The GC risk ratio was 8-times higher in the elderly than in the other age groups (HR=8.0, 2.7-23.5). The incidence of gastric cancer in patients with H. pylori infection was 18-times and that of smokers 2-times higher than other populations. Low level of economic situation and food insecurity increased the odds of GC by 2.42- and 2.57-times, respectively. It should be noted that there was a direct relationship between consumption of processed red meat, dairy products, fruit juice, smoked and salty fish and legumes, strong and hot tea, and consumption of salt and gastric cancer incidence. There was also an inverse relationship between citrus consumption, fresh fruit, garlic, and gastric cancer. In addition, the mRNA genes are the most GC-related genes. CONCLUSION Given the high incidence of GC in Iran, changing lifestyle and decreasing consumption of preservatives in food, increasing consumption of fruits and vegetables, and improving the lifestyle can be effective in reducing the incidence of this disease.
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Affiliation(s)
- Khadijeh Kalan Farmanfarma
- Department of Epidemiology, Health Promotion Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Neda Mahdavifar
- Department of Biostatistics and Epidemiology, School of Health, Non-Communicable Diseases Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Soheil Hassanipour
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Hamid Salehiniya
- Social Determinants of Health Research Center, Birjand University of Medical Sciences, Birjand, Iran
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Bakhti SZ, Latifi‐Navid S, Safaralizadeh R. Helicobacter pylori-related risk predictors of gastric cancer: The latest models, challenges, and future prospects. Cancer Med 2020; 9:4808-4822. [PMID: 32363738 PMCID: PMC7333836 DOI: 10.1002/cam4.3068] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 03/31/2020] [Accepted: 03/31/2020] [Indexed: 12/24/2022] Open
Abstract
Helicobacter pylori is known as an important determinant of preneoplastic lesions or gastric cancer (GC) risk. The bacterial genotypes may determine the clinical outcomes. However, the evidence for these associations has varied between and within continents, and the actual effect of each gene and corresponding allelic variants are still debatable. In recent years, two new models have been proposed to predict the risk of GC; the phylogeographic origin of H. pylori strains and a disrupted co-evolution between H. pylori and its human host, which potentially explain the geographic differences in the risk of H. pylori-related cancer. However, these models and earlier ones based on putative virulence factors of the bacterium may not fully justify differences in the incidence of GC, reflecting that new theories should be developed and examined. Notably, the new findings also support the role of ancestry-specific germline alteration in contributing to the ethnic/population differences in cancer risk. Moreover the high and low incidence areas of GC have shown differences in transmission ecology, largely affecting the composition of H. pylori populations. As a new hypothesis, it is proposed that any high-risk population may have its own specific risk loci (or variants) as well as new H. pylori strains with national/maybe regional gene pools that should be considered. The latter is seen in the Americas where the rapid evolution of distinct H. pylori subpopulations has been occurred. It is therefore proposed that the deep sequencing of both H. pylori and its human host is simultaneously performed in GC patients and age-sex-matched controls from high-risk areas. The expression and functional activities of the identified new determinants of GC must then be assessed and matched with human and pathogen ancestry, because some of risk loci are ancestry-specific. In addition, potential study-level covariates and moderator variables (eg physical conditions, life styles, gastric microbiome, etc) linked to causal relationships, and their impact, should be recognized and controlled.
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Affiliation(s)
- Seyedeh Zahra Bakhti
- Department of BiologyFaculty of SciencesUniversity of Mohaghegh ArdabiliArdabilIran
| | - Saeid Latifi‐Navid
- Department of BiologyFaculty of SciencesUniversity of Mohaghegh ArdabiliArdabilIran
| | - Reza Safaralizadeh
- Department of Animal BiologyFaculty of Natural SciencesUniversity of TabrizTabrizIran
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Korona-Glowniak I, Cichoz-Lach H, Siwiec R, Andrzejczuk S, Glowniak A, Matras P, Malm A. Antibiotic Resistance and Genotypes of Helicobacter pylori Strains in Patients with Gastroduodenal Disease in Southeast Poland. J Clin Med 2019; 8:1071. [PMID: 31330898 PMCID: PMC6678771 DOI: 10.3390/jcm8071071] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 07/15/2019] [Accepted: 07/18/2019] [Indexed: 12/11/2022] Open
Abstract
The aim of this study was to investigate genetic diversity of Helicobacter pylori virulence markers to predict clinical outcome as well as to determine an antibiotic susceptibility of H. pylori strains in Poland. Gastric biopsies from 132 patients with gastrointestinal disorders were tested for presence of H. pylori with the use of rapid urease test, microbial culture, and polymerase chain reaction (PCR) detection. The genetic diversity of 62 H. pylori positive samples was evaluated by detection of cagA and PCR-typing of vacA and iceA virulence-associated genes. Most common H. pylori genotypes were cagA(+)vacAs1m2 (27.4%) and cagA(-)vacAs2m2 (24.2%). In logistic regression analysis, we recognized the subsequent significant associations: gastritis with ureC, i.e., H. pylori infection (p = 0.006), BMI index (p = 0.032); and negatively with iceA1 (p = 0.049) and peptic ulcer with cagA (p = 0.018). Thirty-five H. pylori strains were cultured and tested by E-test method showing that 49% of strains were resistant to at least one of the tested antibiotics. This is the first study that reports the high incidence and diversity of allelic combination of virulence genes in gastroduodenitis patients in Poland. Genotyping of H. pylori strains confirmed the involvement of cagA gene and vacAs1m1 genotype in development and severity of gastric disorder.
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Affiliation(s)
- Izabela Korona-Glowniak
- Department of Pharmaceutical Microbiology with Laboratory for Microbiological Diagnostics, Medical University of Lublin, Chodzki Str. 1, 20-093 Lublin, Poland.
| | - Halina Cichoz-Lach
- Department of Gastroenterology with Endoscopic Unit, Medical University of Lublin, Jaczewskiego Str. 8, 20-090 Lublin, Poland
| | - Radoslaw Siwiec
- Department of Pharmaceutical Microbiology with Laboratory for Microbiological Diagnostics, Medical University of Lublin, Chodzki Str. 1, 20-093 Lublin, Poland
| | - Sylwia Andrzejczuk
- Department of Pharmaceutical Microbiology with Laboratory for Microbiological Diagnostics, Medical University of Lublin, Chodzki Str. 1, 20-093 Lublin, Poland
| | - Andrzej Glowniak
- Department of Cardiology, Medical University of Lublin, 20-090 Lublin, Jaczewskiego Str. 8, 20-090 Lublin, Poland
| | - Przemyslaw Matras
- Chair and Department of General and Transplant Surgery and Nutritional Treatment, Medical University of Lublin, Jaczewskiego Str. 8, 20-090 Lublin, Poland
| | - Anna Malm
- Department of Pharmaceutical Microbiology with Laboratory for Microbiological Diagnostics, Medical University of Lublin, Chodzki Str. 1, 20-093 Lublin, Poland
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Román-Román A, Martínez-Carrillo DN, Atrisco-Morales J, Azúcar-Heziquio JC, Cuevas-Caballero AS, Castañón-Sánchez CA, Reyes-Ríos R, Betancourt-Linares R, Reyes-Navarrete S, Cruz-Del Carmen I, Camorlinga-Ponce M, Cortés-Malagón EM, Fernández-Tilapa G. Helicobacter pylori vacA s1m1 genotype but not cagA or babA2 increase the risk of ulcer and gastric cancer in patients from Southern Mexico. Gut Pathog 2017; 9:18. [PMID: 28413454 PMCID: PMC5390388 DOI: 10.1186/s13099-017-0167-z] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2016] [Accepted: 04/05/2017] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The vacA, cagA and babA2 genotypes of Helicobacter pylori are associated with gastric pathology. The objectives were to determine the frequency of infection and distribution of the vacA, cagA and babA2 genotypes of H. pylori in patients with gastric ulcer, chronic gastritis and gastric cancer, and to evaluate the association of virulent genotypes with diagnosis. METHODS We studied 921 patients with symptoms of dyspepsia or with presumptive diagnosis of gastric cancer. The DNA of H. pylori and the vacA, cagA and babA2 genes was detected by PCR in total DNA from gastric biopsies. The association of H. pylori and of its cagA, vacA and babA2 genotypes with diagnosis was determined by calculating the odds ratio (OR). RESULTS Chronic gastritis was confirmed in 767 patients, gastric ulcer in 115 and cancer in 39. The prevalence of H. pylori was 47.8, 49.6 and 61.5% in those groups, respectively. H. pylori was more frequent in the surrounding tissue (69.2%) than in the tumor (53.8%). The vacA s1m1 genotype predominated in the three groups (45.2, 61.4 and 83.3%, respectively). H. pylori was associated with cancer (ORadjusted = 2.08; 95% CI 1.05-4.13; p = 0.035) but not with ulcer (ORadjusted = 1.07; 95% CI 0.71-1.61; p = 0.728). The s1m1 genotype was associated with ulcer and cancer (ORadjusted = 2.02; 95% CI 1.12-3.62; p = 0.019 and ORadjusted = 6.58; 95% CI 2.15-20.08; p = 0.001, respectively). babA2 was associated with gastric cancer, and cagA was not associated with the diagnosis. CONCLUSIONS In population from Southern Mexico, H. pylori and the s1m1 genotype were associated with gastric cancer and the s1m1/cagA+/babA2+ strains predominated in tumor and adjacent tissue.
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Affiliation(s)
- Adolfo Román-Román
- Laboratorio de Investigación en Bacteriología, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero México
| | - Dinorah Nashely Martínez-Carrillo
- Laboratorio de Investigación Clínica, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Avenida Lázaro Cárdenas S/N Ciudad Universitaria Sur, Col. La Haciendita, 39087 Chilpancingo, Guerrero México
| | - Josefina Atrisco-Morales
- Laboratorio de Investigación Clínica, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Avenida Lázaro Cárdenas S/N Ciudad Universitaria Sur, Col. La Haciendita, 39087 Chilpancingo, Guerrero México
| | - Julio César Azúcar-Heziquio
- Laboratorio de Investigación Clínica, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Avenida Lázaro Cárdenas S/N Ciudad Universitaria Sur, Col. La Haciendita, 39087 Chilpancingo, Guerrero México
| | - Abner Saúl Cuevas-Caballero
- Laboratorio de Investigación Clínica, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Avenida Lázaro Cárdenas S/N Ciudad Universitaria Sur, Col. La Haciendita, 39087 Chilpancingo, Guerrero México
| | | | - Roxana Reyes-Ríos
- Laboratorio de Investigación Clínica, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Avenida Lázaro Cárdenas S/N Ciudad Universitaria Sur, Col. La Haciendita, 39087 Chilpancingo, Guerrero México
| | | | - Salomón Reyes-Navarrete
- Servicio de Endoscopia, Instituto Estatal de Cancerología "Dr. Arturo Beltrán Ortega", Acapulco, Guerrero México
| | - Iván Cruz-Del Carmen
- Servicio de Endoscopia, Hospital General "Dr. Raymundo Abarca Alarcón", Chilpancingo, Guerrero México
| | - Margarita Camorlinga-Ponce
- Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México
| | - Enoc Mariano Cortés-Malagón
- Laboratorio de Biología Molecular del Cáncer, Unidad de Investigación, Hospital Juárez de México, Ciudad de México, México
| | - Gloria Fernández-Tilapa
- Laboratorio de Investigación Clínica, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Avenida Lázaro Cárdenas S/N Ciudad Universitaria Sur, Col. La Haciendita, 39087 Chilpancingo, Guerrero México
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Chmiela M, Karwowska Z, Gonciarz W, Allushi B, Stączek P. Host pathogen interactions in Helicobacter pylori related gastric cancer. World J Gastroenterol 2017; 23:1521-1540. [PMID: 28321154 PMCID: PMC5340805 DOI: 10.3748/wjg.v23.i9.1521] [Citation(s) in RCA: 89] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 10/26/2016] [Accepted: 02/16/2017] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor.
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Thi Huyen Trang T, Thanh Binh T, Yamaoka Y. Relationship between vacA Types and Development of Gastroduodenal Diseases. Toxins (Basel) 2016; 8:toxins8060182. [PMID: 27294955 PMCID: PMC4926148 DOI: 10.3390/toxins8060182] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 05/29/2016] [Accepted: 05/31/2016] [Indexed: 02/07/2023] Open
Abstract
The Helicobacter pylori vacuolating cytotoxin (VacA) is a secreted pore-forming toxin and a major virulence factor in the pathogenesis of H. pylori infection. While VacA is present in almost all strains, only some forms are toxigenic and pathogenic. While vacA and its genotypes are considered as markers of H. pylori-related diseases or disorders, the pathophysiological mechanisms of VacA and its genotypes remain controversial. This review outlines key findings of publications regarding vacA with emphasis on the relationship between vacA genotypes and the development of human disease.
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Affiliation(s)
- Tran Thi Huyen Trang
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu-City, Oita 879-5593, Japan.
- Department of Molecular Biology, 108 Hospital, Hanoi, Vietnam.
| | - Tran Thanh Binh
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu-City, Oita 879-5593, Japan.
- Department of Endoscopy, Cho Ray Hospital, Ho Chi Minh, Vietnam.
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu-City, Oita 879-5593, Japan.
- Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX 77030, USA.
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Moaddeb A, Fattahi MR, Firouzi R, Derakhshandeh A, Farshad S. Genotyping of the Helicobacter pylori cagA Gene Isolated From Gastric Biopsies in Shiraz, Southern Iran: A PCR-RFLP and Sequence Analysis Approach. Jundishapur J Microbiol 2016; 9:e30046. [PMID: 27335631 PMCID: PMC4914860 DOI: 10.5812/jjm.30046] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2015] [Revised: 09/23/2015] [Accepted: 09/23/2015] [Indexed: 01/05/2023] Open
Abstract
Background Cytotoxin-associated gene A (cagA) is an important virulence factor in the pathogenesis of Helicobacter pylori. Objectives The aim of this study was to genotype the H. pylori cagA gene isolated from antral biopsies of patients with stomach symptoms, using a PCR-restriction fragment length polymorphism (PCR-RFLP) analysis. Patients and Methods A total of 161 gastric biopsies were collected from patients with stomach symptoms. After isolation of H. pylori from the biopsy culture, the cagA gene was assessed using PCR. The PCR products were then digested by the HinfI restriction endonuclease enzyme. A sample of each genotype was also subjected to direct sequencing for further analysis. Results From 161 antral biopsies, 61 (37.9%) were positive for H. pylori in culture. Overall, 24 cagA-positives were detected in the isolates. RFLP indicated three different genotypes (I, II, and III) of cagA with a frequency of 62.5%, 25%, and 12.5% among the isolates, respectively. Genotypes I and II of cagA were predominant in patients who had gastritis. However, genotype III was found in three patients with duodenitis and duodenal ulcers. Alignment of the nucleotide sequences of the three isolated genotypes, with H. pylori 26695 as a reference strain, revealed 12 inserted nucleotides in genotype III. When the sequence of genotype III was aligned with 15 additional H. pylori strains available in GenBank, the same inserted nucleotides were detected in six of them. Conclusions Using the PCR-RFLP method, three distinctive H. pylori cagA genotypes were detected in antral biopsies. Genotype I, which was predominant among the isolates, was significantly associated with gastritis. However, the data showed that cagA genotype III may play a role in duodenitis and duodenal ulcers in patients infected with H. pylori.
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Affiliation(s)
- Afsaneh Moaddeb
- Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, IR Iran
| | - Mohammad Reza Fattahi
- Gastroentrohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Roya Firouzi
- Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, IR Iran
| | - Abdollah Derakhshandeh
- Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, IR Iran
| | - Shohreh Farshad
- Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
- Corresponding author: Shohreh Farshad, Clinical Microbiology Research Center, Shiraz University of Medical Sciences, P. O. Box: 7193711351, Shiraz, IR Iran. Tel: +98-7136474304; +98-9173173501, Fax: +98-7136474303, E-mail:
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Zabaglia LM, Ferraz MA, Pereira WN, Orcini WA, de Labio RW, Neto AC, Wisnieski F, de Oliveira JG, de Arruda Cardoso Smith M, Payão SLM, Rasmussen LT. Lack of association among TNF-α gene expression, -308 polymorphism (G > A) and virulence markers of Helicobacter pylori. J Venom Anim Toxins Incl Trop Dis 2015; 21:54. [PMID: 26719751 PMCID: PMC4696262 DOI: 10.1186/s40409-015-0054-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 12/21/2015] [Indexed: 12/18/2022] Open
Abstract
Background Tumor necrosis factor plays a critical role in the pathogenesis of gastric diseases such as gastric cancer, and an abnormal inflammatory response has frequently been observed in dyspeptic patients. Helicobacter pylori infection can induce a gastric mucosal inflammatory response that may be influenced by -308 (G > A) polymorphisms and gene expression of the TNF-α gene. Methods One hundred and thirty-four gastric biopsy samples were collected from patients of both genders (61♂ and 73♀, mean age 40.3 ± 24.2 years) with gastric symptoms. The -308 (G > A) polymorphism of TNF-α was characterized using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The expression level was measured using real-time PCR, and relative quantification (RQ) was calculated using the comparative CT method (2-ΔΔCT). Results The analysis revealed an increase in TNF-α gene expression in patients with gastritis; on the other hand, no statistical differences were observed in patients with gastric cancer. In addition, no association was found among -308 polymorphism genotypes, virulence markers, or TNF-α gene expression. Conclusions Helicobacter pylori induces a large increase in TNF-α expression in patients with gastritis, regardless of tissue inflammation, but after the tissue becomes neoplastic, the presence of bacteria did not influence expression. These results suggest that the TNF-α pathway may play an important role in the progression from gastritis to gastric cancer
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Affiliation(s)
- Luanna Munhoz Zabaglia
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | - Mariane Avante Ferraz
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | - Weendelly Nayara Pereira
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | - Wilson Aparecido Orcini
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil
| | | | | | - Fernanda Wisnieski
- Universidade Federal de São Paulo, Rua Sena Madureira, 1500, 04021-001 São Paulo, SP Brazil
| | | | | | - Spencer Luiz Marques Payão
- Universidade Sagrado Coração, Rua Irmã Arminda 10-50, Jardim Brasil, CEP 17011-160 Bauru, SP Brazil ; Faculdade de Medicina de Marília, Rua Lourival Freire 240, 17519-050 Marília, SP Brazil
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Helicobacter pylori vacA i region polymorphism but not babA2 status associated to gastric cancer risk in northwestern Iran. Clin Exp Med 2014; 16:57-63. [PMID: 25472424 DOI: 10.1007/s10238-014-0327-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Accepted: 11/22/2014] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori-specific genotypes have been strongly associated with an increased risk of gastric cancer (GC). The aim of the present work was to study the associations of H. pylori virulence factors, vacA i region polymorphisms and babA2 status with GC risk in Azerbaijan patients. The DNA extracted from gastric biopsy specimens was used to access the babA2 and vacA genotypes. Overall, babA2 was present in 85.39 % (76/89) of H. pylori strains: 19 out of 24 (79.16 %) strains from GC, 16 out of 17 (94.14 %) strains from peptic ulcer disease (PUD) and 41 out of 48 (85.14 %) strains from chronic gastritis. No significant association was found between babA2 genotype and clinical outcomes (P > 0.05). i1 vacA polymorphism was detected in 46/89 (51.68 %) strains: in 21/24 (87.5 %), 6/17 (35.29 %) and 19/48 (39.58 %) patients with GC, PUD and chronic gastritis, respectively. i2 allele was detected in 43 (48.31 %) out of all 89 strains examined: 3 (14.28 %) of 24 strains from GC, 11 (64.71 %) of 17 from PUD, and 29 (60.42 %) of 48 strains from chronic gastritis. In this study, multiple linear regression analysis confirmed the strong association of i1 allele with GC (partial regression correlation 0.455 ± 0.101; P = 0). Results of multiple logistic regression analysis showed that vacA i1 genotype was significantly associated with GC compared with a control group (gastritis) (odds ratio 13.142, 95 % CI 3.116-55.430; P = 0). Findings from the measurement of H. pylori babA2 and vacA genotypes indicate a strong correlation between the vacA i1 allele and GC risk in the Azerbaijan area of Iran.
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