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Wattanawongdon W, Simawaranon Bartpho T, Tongtawee T. Relationship between Helicobacter pylori virulence genes and gastroduodenal disease. J Int Med Res 2023; 51:3000605231161465. [PMID: 36924226 PMCID: PMC10026102 DOI: 10.1177/03000605231161465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/17/2023] Open
Abstract
OBJECTIVE This study aimed to identify Helicobacter pylori virulence factors and examine their associations with clinical outcomes in Thai patients. Moreover, the association between these genotypes and gastric mucosa morphological patterns was investigated. METHODS This retrospective study enrolled patients who underwent esophagogastroduodenoscopy at Suranaree University of Technology Hospital. The presence of the cagA and vacA genes was investigated by real-time polymerase chain reaction. RESULTS The H. pylori-specific genes ureA and 16S rRNA were detected in all 698 gastric biopsy specimens. In total, 567 (81.23%) patients with H. pylori infection were positive for the cagA gene, 443 (63.46%) were positive for the vacA gene, and 370 (53.0%) were positive for both. The cagA genotype was significantly more common in patients with chronic gastritis and peptic ulcers (78.99% and 79.41%, respectively) than the vacA gene (51.48% and 55.88%, respectively) and combined genotypes (32.34% and 47.05%, respectively). Moreover, the cagA genotype was significantly more common in patients with type 4 or 5 gastric mucosa patterns (69.49% and 76.31%, respectively). CONCLUSIONS The cagA genotype is the main cause of serious inflammation of the gastric mucosa. The cagA gene is possibly an important factor explaining gastroduodenal disease outcomes in Thai patients with H. pylori infection.
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Affiliation(s)
- Wareeporn Wattanawongdon
- School of Surgery, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima, Thailand
- Translational Medicine Programs, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima, Thailand
| | - Theeraya Simawaranon Bartpho
- Translational Medicine Programs, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima, Thailand
- School of Pathology, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima, Thailand
| | - Taweesak Tongtawee
- School of Surgery, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima, Thailand
- Translational Medicine Programs, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima, Thailand
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Niknam R, Fattahi MR, Sepehrimanesh M, Safarpour A. Prevalence of Helicobacter pylori in Southern Part of Iran. Jundishapur J Microbiol 2018; 11. [DOI: 10.5812/jjm.62379] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2023] Open
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Bagheri N, Azadegan-Dehkordi F, Rafieian-Kopaei M, Rahimian G, Asadi-Samani M, Shirzad H. Clinical relevance of Helicobacter pylori virulence factors in Iranian patients with gastrointestinal diseases. Microb Pathog 2016; 100:154-162. [PMID: 27666510 DOI: 10.1016/j.micpath.2016.09.016] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Revised: 09/21/2016] [Accepted: 09/21/2016] [Indexed: 12/21/2022]
Abstract
Helicobacter pylori (H. pylori) usually colonizes the gastric mucosa of more than 50% of the human population, causing an infection that may appear in early childhood and can persist for life. H. pylori is suggested as the main cause of peptic ulcer and chronic gastritis. It is also associated with gastric cancer. Its severity and symptoms depend on environmental factors, host susceptibility and bacterial components, which allow H. pylori to switch between commensalism and pathogenicity. H. pylori is genetically highly variable, and the variability which affects H. pylori virulence factors might be useful in identifying the strains with different degrees of pathogenicity. The geographic distribution of distinct H. pylori genotypes is largely unknown and should be established. The prevalence of more pathogenic genotypes in certain areas may have important epidemiological consequences. It also might be associated with the severity of H. pylori related diseases in such regions. Given that Iran is located in the Middle East and Asian populations have revealed high levels of gastric cancer, it is of clinical interest to clarify the potential of H. pylori virulence markers in predicting the associated clinical outcomes. In this review, clinical relevance of adhesion molecules and significant virulence factors of H. pylori in Iranian patients with gastrointestinal diseases are discussed in comparison to other countries.
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Affiliation(s)
- Nader Bagheri
- Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran; Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | | | | | - Ghorbanali Rahimian
- Department of Internal Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Majid Asadi-Samani
- Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Hedaytollah Shirzad
- Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
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Ranjbar R, Khamesipour F, Jonaidi-Jafari N, Rahimi E. Helicobacter pylori isolated from Iranian drinking water: vacA, cagA, iceA, oipA and babA2 genotype status and antimicrobial resistance properties. FEBS Open Bio 2016; 6:433-441. [PMID: 27419049 PMCID: PMC4856422 DOI: 10.1002/2211-5463.12054] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 03/09/2016] [Accepted: 03/10/2016] [Indexed: 02/05/2023] Open
Abstract
Despite the clinical importance of Helicobacter pylori in human gastric disorders, its exact route of transmission is still uncertain. Based on the contentious hypothesis and findings of previous investigations, water may play an important role in the transmission of H. pylori to humans. This study was carried out to investigate the vacA, cagA, oipA, iceA and babA2 genotype status and antimicrobial resistance properties of H. pylori strains isolated from the drinking water samples of four major provinces in Iran. A total of 400 drinking water samples were cultured and tested. H. pylori-positive strains were analyzed for the presence of various genotypes and antimicrobial resistance. Twelve of 400 (3%) water samples were positive for H. pylori. Samples from Isfahan province had the highest, while those from Shiraz had the lowest prevalence of H. pylori. The seasonal distribution was also determined, with the highest prevalence of bacteria in the summer season (7.36%). H. pylori strains harbored the highest levels of resistance against ampicillin (100%), erythromycin (75%), clarithromycin (75%), and trimethoprim (58.3%). The most commonly detected genotypes were vacAs1a (83.3%), vacAm1a (66.6%), vacAs2 (50%) and cagA (50%). The presence of similar genotypes in the H. pylori strains of drinking water and those of human clinical samples suggest that contaminated water maybe the sources of bacteria. Spiramycin and furazolidone are suggested for the treatment of cases of H. pylori infection.
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Affiliation(s)
- Reza Ranjbar
- Molecular Biology Research Center Baqiyatallah University of Medical Sciences Tehran Iran
| | - Faham Khamesipour
- Cellular and Molecular Research Center Sabzevar University of Medical Sciences Sabzevar Iran
| | | | - Ebrahim Rahimi
- Department of Food Hygiene Faculty of Veterinary Medicine Shahrekord Branch Islamic Azad University Shahrekord Iran
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Ranjbar R, Khamesipour F, Jonaidi-Jafari N, Rahimi E. Helicobacter pylori in bottled mineral water: genotyping and antimicrobial resistance properties. BMC Microbiol 2016; 16:40. [PMID: 26970903 PMCID: PMC4789264 DOI: 10.1186/s12866-016-0647-1] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Accepted: 02/29/2016] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Up to now, fecal-oral and oral-oral are the most commonly known routes for transmission of H. pylori, therefore, contaminated water can play an important role in transmission of H. pylori to humans. Genotyping using virulence markers of H. pylori is one of the best approaches to study the correlations between H. pylori isolates from different samples. The present research was carried out to study the vacA, cagA, cagE, oipA, iceA and babA2 genotyping and antimicrobial resistance properties of H. pylori isolated from the bottled mineral water samples of Iran. RESULTS Of 450 samples studied, 8 samples (1.77%) were contaminated with H. pylori. Brand C of bottled mineral water had the highest prevalence of H. pylori (3.63%). The bottled mineral water samples of July month had the highest levels of H. pylori-contamination (50%). H. pylori strains had the highest levels of resistance against metronidazole (62.5%), erythromycin (62.5%), clarithromycin (62.5%), amoxicillin (62.5%) and trimethoprim (62.5%). Totally, 12.5% of strains were resistant to more than 6 antibiotics. VvacAs1a (100%), vacAm1a (87.5%), cagA (62.5%), iceA1 (62.5%), oipA (25%), babA2 (25%) and cagE (37.5%) were the most commonly detected genotypes. M1as1a (62.5%), m1as2 (37.5%), m2s2 (37.5%) and S1a/cagA+/IceA2/oipA-/babA2-/cagE- (50%) were the most commonly detected combined genotypes. CONCLUSIONS Contaminated bottled mineral water maybe the sources of virulent and resistant strains H. pylori. Careful monitoring of bottled mineral water production may reduce the risk of H. pylori transmission into the human population.
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Affiliation(s)
- Reza Ranjbar
- />Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Faham Khamesipour
- />Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | | | - Ebrahim Rahimi
- />Department of Food Hygiene, Faculty of Veterinary Medicine, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
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Clinical Outcome of Eradication Therapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma according to H. pylori Infection Status. Gastroenterol Res Pract 2016; 2016:6794848. [PMID: 27034656 PMCID: PMC4789472 DOI: 10.1155/2016/6794848] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Accepted: 02/07/2016] [Indexed: 12/21/2022] Open
Abstract
Background. To evaluate the long-term outcome of H. pylori eradication therapy for gastric MALT lymphoma according to the presence of H. pylori infection. Methods. We retrospectively reviewed the medical records of patients between January 2001 and June 2014. The clinicopathologic characteristics and clinical outcomes were compared between H. pylori-positive and H. pylori-negative gastric MALT lymphoma groups. Results. Fifty-four patients were enrolled: 12 H. pylori-negative and 42 H. pylori-positive patients. The tumor was located more frequently in both the proximal and distal parts of the stomach (P = 0.001), and the percentage of multiple lesions was significantly greater in the H. pylori-negative group (P = 0.046). Forty-seven patients received initial eradication therapy, and 85% (35/41) of H. pylori-positive patients and 50% (3/6) of H. pylori-negative patients achieved complete remission after eradication therapy. The presence of multiple lesions was a predictive factor for unresponsiveness to H. pylori eradication (P = 0.024). The efficacy of eradication therapy (P = 0.133), complete remission (CR) maintenance period, and relapse after eradication therapy were not significantly different between the two groups. Conclusions. H. pylori eradication therapy could be an effective first-line treatment for localized H. pylori-negative gastric MALT lymphoma, especially for single lesions.
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Honarmand-Jahromy S, Siavoshi F, Malekzadeh R, Nejad Sattari T, Latifi-Navid S. Reciprocal impact of host factors and Helicobacter pylori genotypes on gastric diseases. World J Gastroenterol 2015; 21:9317-9327. [PMID: 26309357 PMCID: PMC4541383 DOI: 10.3748/wjg.v21.i31.9317] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2015] [Revised: 03/22/2015] [Accepted: 05/07/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the impact of Helicobacter pylori (H. pylori) genotypes and patient age and sex on the development of gastric diseases. METHODS H. pylori-infected patients (n = 233) referred to the endoscopy unit at Tehran University of Medical Sciences (Tehran, Iran) were diagnosed with chronic gastritis (CG), gastric ulcer (GU), or duodenal ulcer (DU). Brucella blood agar was used for biopsy cultures and H. pylori isolation under microaerobic conditions. H. pylori isolates were confirmed with biochemical tests and through amplification of the 16S rRNA gene. DNA was extracted from fresh cultures of the H. pylori isolates and used for amplification of vacA alleles and the cagA gene. Statistical analysis was performed to determine the association between H. pylori genotypes, age (< 40 years vs > 40 years) and sex of the patient, and gastric diseases. RESULTS CG was the most prevalent gastric disease (113/233; 48.5%), compared to GU (64/233; 27.5%) and DU (56/233; 24%). More patients were male, and gastric diseases were more frequent in patients > 40 years (P < 0.05). The percentage of CG and GU patients that were male and female did not show a significant difference; however DU was more common in males (P < 0.05). Interestingly, a diagnosis of CG in patients > 40 years was more common in females (18.5%) than males (11.6%) (P = 0.05), whereas a diagnosis of GU or DU in patients > 40 years was more frequent in males (14.6% vs 10.7% and 12.4% vs 4.3%, respectively). Overall, genotyping of the H. pylori isolates revealed that the vacA s1 (82%), vacA m2 (70%), and cagA (+) (72.5%) alleles were more frequent than vacA s2 (18%), vacA m1 (29.2%), and cagA(-) (all P < 0.05). The vacA s1m2cagA (+) genotype was the most prevalent within the three disease groups. vacA s1m2 frequency was 56.2% with a similar occurrence in all diagnoses, while vacA s1m1 appeared more often in DU patients (33.9%). A genotype of vacA s2m2 occurred in 15% of isolates and was more common in CG patients (21.2%); vacA s2m1 was the least common genotype (3%). The vacA s1 allele was found to be a risk factor for DU, vacA s2 for CG, and vacA s1 and vacA s2 for GU (all P < 0.05). The vacA s2m2 genotype was associated with the development of CG and GU compared to DU (P < 0.05). No correlation was found between vacA m or cagA and gastric diseases. CONCLUSION The outcome of H. pylori infection is the result of interaction between bacterial genotypes and the age and sex of infected individuals.
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Alikhani MY, Arebestani MR, Sayedin Khorasani M, Majlesi A, Jaefari M. Evaluation of Helicobacter pylori vacA and cagA Genotypes and Correlation With Clinical Outcome in Patients With Dyspepsia in Hamadan Province, Iran. IRANIAN RED CRESCENT MEDICAL JOURNAL 2014; 16:e19173. [PMID: 25763216 PMCID: PMC4329959 DOI: 10.5812/ircmj.19173] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/29/2014] [Revised: 06/14/2014] [Accepted: 07/09/2014] [Indexed: 01/04/2023]
Abstract
Background: Helicobacter pylori is known to be a causative agent of chronic active gastritis, peptic ulcer and gastric cancer in human. Diverse genotypes of H. pylori strains have different virulence potency and geographic distribution. Objectives: The purpose of this study was to investigate the association between the cytotoxin-associated gene (cagA), and the various vacuolating cytotoxin (vacA) genotypes of H. pylori strains and clinical outcomes in patients referred to Shahid-Beheshti Hospital in Hamadan, Iran. Patients and Methods: In this cross-sectional study, biopsy samples were collected consecutively from 153 patients with gastric cancer (GC), peptic ulcer dyspepsia (PUD) and non-ulcer dyspepsia (NUD) in the gastroenterology department of Shahid-Beheshti Hospital in Hamadan province, the west of Iran. H. pylori infection was confirmed in 83 patients (3 with GC, 27 with PUD, and 53 with NUD) by histology, rapid urease test (RUT) and culture. Genomic DNA was extracted from the bacterial isolate and was further confirmed with 16S rRNA gene sequencing as H. pylori, and characterized based on cagA and vacA genotyping using the polymerase chain reaction (PCR) method. Results: In this study, vacA genotypes s1/m2, s1/m1, s2/m2 and s2/m1 were determined in 43.4%, 19.3%, 13.2% and 6% of the isolated H. pylori, respectively. The vacAs1 genotype was detected in 52 (62.6%) isolates, of which the vacAs1a genotype was detected in 45.2, 40.7, and 66.6% of the isolates from patients with NUD, PUD, and GC, respectively. The cagA-positive genotype was determined in 73 (87.9%) isolates and 10 (12.1%) were negative. The frequency rates of cagA gene were 84.9, 92.6 and 100% in isolates of patients with NUD, PUD, and GC, respectively. The cagA-positive genotype is strongly associated with s1a/m2 and s1a/m1 vacA genotypes. Conclusions: The most predominant VacA genotypes in our areas were s1/m2 and s1/m1, which regard as the genotypes with more virulence intensity. The H. pylorivacAs1a, cagA genotypes have a significant relationship with the presence of PUD and GC in Iranian patients with dyspepsia.
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Affiliation(s)
- Mohammad Yousef Alikhani
- Brucellosis Research Center, Hamadan University of Medical Sceinces, Hamadan, IR Iran
- Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IR Iran
| | - Mohammad Reza Arebestani
- Brucellosis Research Center, Hamadan University of Medical Sceinces, Hamadan, IR Iran
- Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IR Iran
- Corresponding Author: Mohammad Reza Arebestani, Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IR Iran. Tel: +98-9188662009, Fax: +98-8118380762, E-mail:
| | - Masood Sayedin Khorasani
- Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IR Iran
| | - Amir Majlesi
- Department of Gastrointestinal Diseases, Beheshti Hospital, Hamadan University of Medical Sciences, Hamadan, IR Iran
| | - Mohammad Jaefari
- Department of Pathology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IR Iran
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Zhang BB, Li Y, Liu XQ, Wang PJ, Yang B, Bian DL. Association between vacA genotypes and the risk of duodenal ulcer: a meta-analysis. Mol Biol Rep 2014; 41:7241-54. [PMID: 25063579 DOI: 10.1007/s11033-014-3610-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2013] [Accepted: 07/12/2014] [Indexed: 12/20/2022]
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Sayehmiri F, Darvishi Z, Sayehmiri K, Soroush S, Emaneini M, Zarrilli R, Taherikalani M. A Systematic Review and Meta-Analysis Study to Investigate the Prevalence of Helicobacter pylori and the Sensitivity of its Diagnostic Methods in Iran. IRANIAN RED CRESCENT MEDICAL JOURNAL 2014; 16:e12581. [PMID: 25068041 PMCID: PMC4102974 DOI: 10.5812/ircmj.12581] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/29/2013] [Revised: 12/14/2013] [Accepted: 04/27/2014] [Indexed: 01/22/2023]
Abstract
CONTEXT Helicobacter pylori is the most common infecting organism affecting humans, being almost half the population infected. The aim of this study was to find out the epidemiological features and the sensitivity of diagnostic methods of Helicobacter pylori infection in Iran, which can provide the logic of developing preventive approaches to control Helicobacter pylori infections and the associated diseases. EVIDENCE ACQUISITION By reviewing the databases of SID, MAGIRAN, SCOPUS, MEDLIB, Google, ISI and PUBMED, a total of 30 papers, published from 1994 to 2011, were extracted. Summary prevalence and 95% confidence intervals (95% CI) were calculated using random-effects model. Statistical analyses were performed using STATA Ver.11. RESULTS Among the 30 studies evaluated, the prevalence rate of Helicobacter pylori infections in Iran was estimated as 50.7 % (95% CI: 44.4-56.9%). When the sensitivity of diagnostic methods was evaluated, ELISA, with an accuracy rate of 52.3% (95% CI: 43.8 to 60.8%) was found the most accurate diagnostic method available. The highest and the least Helicobacter pylori prevalence were 19.2% in Tehran and 74.27% in Mazandran respectively. CONCLUSIONS About half the population in Iran is infected with Helicobacter pylori, the pollution in different areas and preventive strategies should be carried out to control this infection. The prevalence rate of Helicobacter pylori infections in Iran showed only little changes during the years 1994 to 2011.
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Affiliation(s)
- Fatemeh Sayehmiri
- Student Research Commitee, Ilam University of Medical Sciences, Ilam, IR Iran
| | - Zahra Darvishi
- Student Research Commitee, Ilam University of Medical Sciences, Ilam, IR Iran
| | - Kourosh Sayehmiri
- Prevention of Psychosocial Injuries Research Center, Ilam University of Medical Sciences, Ilam, IR Iran
| | - Setareh Soroush
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran ; Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, IR Iran
| | - Mohammad Emaneini
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Raffaele Zarrilli
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Morovat Taherikalani
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, IR Iran
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Rahimian G, Sanei MH, Shirzad H, Azadegan-Dehkordi F, Taghikhani A, Salimzadeh L, Hashemzadeh-Chaleshtori M, Rafieian-Kopaei M, Bagheri N. Virulence factors of Helicobacter pylori vacA increase markedly gastric mucosal TGF-β1 mRNA expression in gastritis patients. Microb Pathog 2014; 67-68:1-7. [PMID: 24462401 DOI: 10.1016/j.micpath.2013.12.006] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2013] [Revised: 12/14/2013] [Accepted: 12/30/2013] [Indexed: 12/23/2022]
Abstract
OBJECTIVE Helicobacter pylori (H. pylori) infection is the main cause of gastric inflammation. Regulatory T cells (Treg cells) suppress the activation and proliferation of antigen-specific T cells and mediate immunologic tolerance. TGF-β1 was shown to be secreted in a subset of Treg cells known as 'Th3 cells'. These cells have not been sufficiently studied in context to H. pylori-induced inflammation in human gastric mucosa. In this study we therefore, aimed to investigate the expression of TGF-β1 in the context of H. pylori colonization in chronic gastritis, to examine the relationship between it and histopathologic findings and to compare it with virulence factors. PATIENTS AND METHODS Total RNA was extracted from gastric biopsies of 48 H. pylori-infected patients and 38 H. pylori-negative patients with gastritis. Mucosal TGF-β1 mRNA expression in H. pylori-infected and uninfected gastric biopsies was determined by real-time PCR. Presence of vacA, cagA, iceA, babA2 and oipA virulence factors was evaluated using PCR. RESULTS TGF-β1 mRNA expression was significantly increased in biopsies of H. pylori-infected patients compared to H. pylori-uninfected patients. There was association between virulence factors and TGF-β1 mRNA expression. TGF-β1 mRNA expression in mucosa was significantly higher in patients with vacA s1 and s1m1. CONCLUSIONS TGF-β1 may play an important role in the inflammatory response and promote the chronic and persistent inflammatory changes in the gastric. This may ultimately influence the outcome of H. pylori-associated diseases that arise within the context of gastritis and vacA may suffice to induce expression of TGF-β1 mRNA.
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Affiliation(s)
- Ghorbanali Rahimian
- Department of Internal Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | | | - Hedayatollah Shirzad
- Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
| | | | - Afshin Taghikhani
- Department of Internal Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Loghman Salimzadeh
- Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | | | | | - Nader Bagheri
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
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Havaei SA, Mohajeri P, Khashei R, Salehi R, Tavakoli H. Prevalence of Helicobacter pylori vacA different genotypes in Isfahan, Iran. Adv Biomed Res 2014; 3:48. [PMID: 24627856 PMCID: PMC3949348 DOI: 10.4103/2277-9175.125761] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2012] [Accepted: 07/21/2012] [Indexed: 01/23/2023] Open
Abstract
Background: It is believed that the Helicobacter pylori (H. pylori) vacA gene, as a major virulence determinant (One of the major virulence determinant, not major), may be a risk factor for the development of gastroduodenal diseases. The frequency of vacA genotypes varies in different human populations. This study evaluated the prevalence of vacA alleles/genotypes among dyspeptic patients in Isfahan. Materials and Methods: One-hundred H. pylori-positive adult patients were examined in this study. After culture of gastric biopsies and DNA extraction from individual H. pylori isolates, the (all H. pylori strains harbor vacA alleles, please replace “presence” with “genotypes”) of the vacA s and m alleles were determined using polymerase chain reaction (PCR). Results: There were four vacA mosaicisms, including 28 for s1a/m1 (28%), 23 for s1b/m1 (23%), 26 for s1a/m2 (26%) and 23 for s1b/m2 (23%). The s2 allele was not found. The predominant vacA genotype in patients with non-ulcer dyspepsia and duodenal ulcer was s1a/m2, whereas in patients with adenocarcinoma was s1a/m1. Conclusion: The results showed there was no significant correlation between different genotypes of the vacA and the clinical outcomes and appears to vacA genotypes were not useful determinants for gastrointestinal diseases in our area.
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Affiliation(s)
- S Asghar Havaei
- Department of Microbiology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
| | - Parviz Mohajeri
- Department of Microbiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Reza Khashei
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Rasoul Salehi
- Department of Cell Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hamid Tavakoli
- Department of Gastroenterology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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Abstract
BACKGROUND CagA+ and vacuolizing cytotoxin (VacA)-specific strains of Helicobacter pylori have been associated with different risks for developing gastric lesions. We aim to summarize a possible association between these genotypes and the risk for developing different gastric phenotypes. MATERIALS AND METHODS A MEDLINE database (PubMed) search was performed and a meta-analysis conducted. RESULTS Forty-four studies were retrieved, all with either a case-control (n=13) or cross-sectional (n=31) design, including 17 374 patients. CagA positivity was associated with an increased risk for gastric cancer [odds ratio (OR) 2.09 (95% confidence interval (CI), 1.48-2.94)] compared with that in individuals without gastric lesions [OR 2.44 (95% CI 1.27-4.70)] and in those with previously identified gastritis. In addition, there was an increased risk for peptic ulcer disease [OR 1.69 (95% CI 1.12-2.55)]. Individuals harboring the H. pylori strains VacA s1 (vs. s2), m1 (vs. m2), s1m1 (vs. s1m2), and s1m1 (vs. s2m2) had an increased risk for development of cancer [OR of 5.32 (95% CI 2.76-10.26), 2.50 (95% CI 1.67-3.750), 2.58 (95% CI 1.24-5.38), and 4.36 (95% CI 2.08-9.10), respectively]. s1m1 strains (vs. s2m2) were also associated with peptic ulcer disease [OR 2.04 (1.01-4.13)]. CONCLUSION Our results indicate that individuals infected with CagA+ H. pylori strains and those infected with VacA s1 and m1 strains have an increased risk for gastric cancer. Cohort studies are welcome to integrate this information in the management of at-risk individuals such as those with precancerous cancer conditions and/or a family history of gastric cancer.
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14
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Rezaeifar A, Eskandari-Nasab E, Moghadampour M, Kharazi-Nejad E, Hasani SSA, Asadi-Saghandi A, Hadadi-Fishani M, Sepanjnia A, Sadeghi-Kalani B. The association of interleukin-18 promoter polymorphisms and serum levels with duodenal ulcer, and their correlations with bacterial CagA and VacA virulence factors. ACTA ACUST UNITED AC 2013; 45:584-92. [PMID: 23746337 DOI: 10.3109/00365548.2013.794301] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND We analyzed the impact of interleukin (IL)-18 promoter polymorphisms on IL-18 serum levels in Helicobacter pylori-infected duodenal ulcer (DU) patients and healthy asymptomatic (AS) carriers. We also aimed to determine the association of the H. pylori virulence factors CagA and VacA antibodies with serum concentrations of IL-18 in order to elucidate any correlation between them. METHODS Three groups of patients were enrolled: DU patients (67 individuals), AS carriers (48 individuals), and H. pylori-negative subjects (26 individuals). Serum concentrations of IL-18 were determined by ELISA. Patient sera were tested by Western blot method to determine the presence of serum antibodies to bacterial CagA and VacA. Genotyping of IL-18 promoter polymorphisms at positions - 137G/C and - 607C/A were performed by allele-specific primer PCR protocol. RESULTS Our study revealed that serum IL-18 levels are positively influenced by CagA-positive H. pylori strains, so that maximum levels of IL-18 were detected in DU patients with the CagA(+) phenotype, regardless of the presence of the anti-VacA antibody. Regarding IL-18 promoter polymorphisms, the AA genotype and A allele at position - 607C/A were found to be significantly lower in DU patients than in AS carriers and H. pylori-negative subjects (p = 0.032 and 0.043, respectively). CONCLUSIONS The IL-18 - 607C variant was associated with higher levels of serum IL-18 and an increased risk of DU. Moreover, our findings indicated that serum concentrations of IL-18 were influenced by CagA factor, irrespective of the VacA status, suggesting that high levels of IL-18 in CagA-positive subjects predisposes to susceptibility to DU.
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Affiliation(s)
- Alireza Rezaeifar
- Department of Clinical Biochemistry, School of Medicine, Zabol University of Medical Sciences, Zabol, Iran
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15
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Ghotaslou R, Milani M, Akhi MT, Nahaei MR, Hasani A, Hejazi MS, Meshkini M. Diversity of Helicobacter Pylori cagA and vacA Genes and Its Relationship with Clinical Outcomes in Azerbaijan, Iran. Adv Pharm Bull 2013; 3:57-62. [PMID: 24312813 DOI: 10.5681/apb.2013.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2012] [Revised: 10/07/2012] [Accepted: 10/07/2012] [Indexed: 12/11/2022] Open
Abstract
PURPOSE The purpose of this research was to analyze cagA and vacA genotypes status in H. pylori isolates and relationship with clinical outcomes. METHODS Gastric biopsy specimens were cultured for H. pylori isolation and cagA and vacA genes were detected in these isolates. Data were collected and the results were analyzed using χ2 and Fishers exact tests by SPSS software version. 16. RESULTS Of the total 115 H. pylori isolates, 79 (68.7 %) were cagA positive and 82 (71.3%) of isolates contained the s1 allele which 33 (28.7%) were subtype s2. s1m2 was the most frequent vacA allelic combination in the H. pylori isolates examined (63 cases), followed by s2m2 (31 cases), s1m1 (19 cases) and s2m1 (2 case). Strains cagA positive were more frequent in peptic ulcer diseases patients than non ulcer diseases patients, as 47 (59.5%) and 32 (40.5%), while cagA negative were low, as 15 (41.7%) and 21 (58.3%), respectively. CONCLUSION We found that the cagA and vacA status were not related to clinical outcomes in this area. Overall, in the present study, vacA s1/m2, cagA-positive strains were predominant irrespective of clinical outcome, but s2/m1 was rare.
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Affiliation(s)
- Reza Ghotaslou
- Liver and Gastroenterology Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. ; Department of Microbiology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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16
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Eskandari-Nasab E, Sepanjnia A, Moghadampour M, Hadadi-Fishani M, Rezaeifar A, Asadi-Saghandi A, Sadeghi-Kalani B, Manshadi MD, Pourrajab F, Pourmasoumi H. Circulating levels of interleukin (IL)-12 and IL-13 in Helicobacter pylori-infected patients, and their associations with bacterial CagA and VacA virulence factors. ACTA ACUST UNITED AC 2012; 45:342-9. [PMID: 23163894 DOI: 10.3109/00365548.2012.737930] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The aim of this study was to determine the association of the Helicobacter pylori virulence factors, cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) antibodies, with serum levels of interleukin (IL)-12 and IL-13 in H. pylori-infected duodenal ulcer (DU) patients and H. pylori-infected asymptomatic (AS) carriers in order to elucidate any correlation between them. METHODS A total of 67 DU patients, 48 AS individuals, and 26 healthy H. pylori-negative subjects were enrolled in this study. Serum concentrations of IL-12 and IL-13 were determined by enzyme-linked immunosorbent assay (ELISA) method. Patient sera were tested by Western blot method to determine the presence of serum antibodies to bacterial virulence antigens p120 (CagA) and p95 (VacA). Serum concentrations of IL-12 and IL-13 were compared in 9 groups, including 4 AS phenotypes (CagA⁺VacA⁺, CagA⁺VacA⁻, CagA⁻VacA⁺, CagA⁻VacA⁻), 4 DU phenotypes (CagA⁺VacA⁺, CagA⁺VacA⁻, CagA⁻VacA⁺, CagA⁻VacA⁻), and 1 control group. RESULTS The results revealed that DU patients positive for CagA, independent of the anti-VacA antibody status, showed drastically elevated levels of IL-12 (251 ± 43 pg/ml) when compared with the other groups (p = 0.0001). No significant difference was found between groups regarding levels of IL-13 (p > 0.05). CONCLUSIONS Our findings indicate that in the DU group, the serum concentrations of IL-12 but not of IL-13 were influenced by bacterial CagA, independent of the VacA status, suggesting that high IL-12 levels may contribute to susceptibility to DU in CagA-positive individuals. These findings could possibly be considered to improve the predictive or prognostic values of inflammatory cytokines for DU, and also to design possible novel therapeutic approaches.
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Affiliation(s)
- Ebrahim Eskandari-Nasab
- Infectious Diseases and Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
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Cho KY, Cho MS, Seo JW. FOXP3+ regulatory T cells in children with helicobacter pylori infection. Pediatr Dev Pathol 2012; 15:118-26. [PMID: 22260624 DOI: 10.2350/11-06-1046-oa.1] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Despite an intensive pro-inflammatory response, the immune system is unable to clear the organism in Helicobacter pylori gastritis. Regulatory T (Treg) cells, which suppress the immune response of antigen-specific T cells, have recently been demonstrated to play a key role in chronic inflammation by immunologic tolerance. The purpose of our study was to investigate the histopathology, FOXP3+CD4+CD25(high)Treg (FOXP3+Treg) cell expression, and immune responses in children with H. pylori infection. Twenty-four H. pylori -positive and 24 H. pylori -negative children who underwent esophagogastroduodenoscopy for dyspeptic symptoms were included. Histopathologic grading according to the updated Sydney classification and immunohistochemical stains for FOXP3, transforming growth factor-β1 (TGF-β1), and CD4 were performed. Histopathologic bacterial density score, gastritis activity score, and chronic inflammation score were higher in the H. pylori -positive group than in the negative group (P < 0.01). The number of FOXP3+Treg cells and CD4+T cells and the grade of TGF-β1 expression were significantly increased in the H. pylori -positive group compared to the negative group (P < 0.01). The number of FOXP3+Treg cells correlated positively with the grade of TGF-β1 expression regardless of H. pylori status (P < 0.05). The number of FOXP3+Treg cells and the grade of TGF-β1 expression correlated positively with H. pylori density, gastritis activity score, and chronic inflammation score regardless of H. pylori status (P < 0.01). These findings indicate that FOXP3+Treg cells could play a role in persistent H. pylori infection.
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Affiliation(s)
- Ky Young Cho
- Department of Pediatrics, Ewha Womans University School of Medicine, Seoul 158-710, Korea
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18
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Khodaii Z, Ghaderian SMH, Akbarzadeh Najar R, Nejati H, Tabatabaei Panah AS. cagA and vacA status and influence of Helicobacter pylori infection on serum oxidative DNA damage in Iranian patients with peptic ulcer disease. Ir J Med Sci 2010; 180:155-61. [PMID: 20721697 DOI: 10.1007/s11845-010-0548-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2010] [Accepted: 08/02/2010] [Indexed: 12/21/2022]
Abstract
BACKGROUND Infection with Helicobacter pylori strains may result in different pathological manifestations and increased oxidative stress leading to a strong inflammatory response in gastric mucosa. AIMS The prevalence of cagA and vacA genes, proteins and the association of serum levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) with oxidative DNA damage were determined. METHODS The presence of cagA gene and vacA alleles and IgG antibodies against CagA and VacA proteins were determined. Oxidative DNA damage status was determined using serum levels of 8-OHdG. RESULTS Helicobacter pylori-positive, cagA-positive, and vacA alleles (s1 and m2) were predominant in all clinical outcomes. There was no significant association between prevalence of CagA and VacA status and clinical outcomes. The serum levels of 8-OHdG was at a higher level in H. pylori-positive patients. CONCLUSIONS These virulence factors are not associated with the development of PUD in Iranian patients. H. pylori infection may be associated with increased serum 8-OHdG.
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Affiliation(s)
- Z Khodaii
- Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences and Health Services, Tehran, Iran
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Shokrzadeh L, Baghaei K, Yamaoka Y, Dabiri H, Jafari F, Sahebekhtiari N, Tahami A, Sugimoto M, Zojaji H, Zali MR. Analysis of 3'-end variable region of the cagA gene in Helicobacter pylori isolated from Iranian population. J Gastroenterol Hepatol 2010; 25:172-177. [PMID: 19793167 PMCID: PMC2818463 DOI: 10.1111/j.1440-1746.2009.05979.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIMS The 3' region of the cagA gene, the most well-known virulence factor of Helicobacter pylori, contains Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs. Four segments flanking the EPIYA motifs, EPIYA-A, -B, -C, or -D, were reported to play important roles in H. pylori-related gastroduodenal pathogenesis. The aim was to determine the roles of EPIYA segments in gastroduodenal pathogenesis in an Iranian population. METHODS A total of 92 cagA-positive Iranian strains isolated from dyspepsia patients with non-ulcer dyspepsia (n = 77), peptic ulcer (n = 11) and gastric cancer (n = 4) were studied. The EPIYA motif genotyping was determined by polymerase chain reaction and sequencing. RESULTS A total of 86 (93.5%) strains had three copies of EPIYA (ABC type), three (3.3%) had four copies (ABCC type) and three (3.3%) had two copies (AB type). The alignment of the deduced protein sequences confirmed that there were no East Asian type EPIYA-D sequences (EPIYATIDFDEANQAG) in Iranian strains. When the prevalence of strains with multiple EPIYA-C segments in Iran was compared with previously published data, it was much lower than that in Colombia and Italy, but was higher than that of Iraq, and the patterns were parallel to the incidence of gastric cancer in these countries. CONCLUSION The structure of the 3' region of the cagA gene in Iranian strains was Western type. Although we could not find differences between EPIYA types and clinical outcomes, low prevalence of strains with multiple EPIYA-C segments might be reasons for low incidence of gastric cancer in Iran.
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Affiliation(s)
- Leila Shokrzadeh
- Research Center of Gastroenterology and Liver Diseases, Shahid Beheshti University, M.C., Tehran, Iran
| | - Kaveh Baghaei
- Research Center of Gastroenterology and Liver Diseases, Shahid Beheshti University, M.C., Tehran, Iran
| | - Yoshio Yamaoka
- Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas, USA
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan
| | - Hossein Dabiri
- Research Center of Gastroenterology and Liver Diseases, Shahid Beheshti University, M.C., Tehran, Iran
| | - Fereshteh Jafari
- Research Center of Gastroenterology and Liver Diseases, Shahid Beheshti University, M.C., Tehran, Iran
| | - Navid Sahebekhtiari
- Research Center of Gastroenterology and Liver Diseases, Shahid Beheshti University, M.C., Tehran, Iran
| | - Ali Tahami
- Research Center of Gastroenterology and Liver Diseases, Shahid Beheshti University, M.C., Tehran, Iran
| | - Mitsushige Sugimoto
- Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas, USA
| | - Homayon Zojaji
- Research Center of Gastroenterology and Liver Diseases, Shahid Beheshti University, M.C., Tehran, Iran
| | - Mohammad Reza Zali
- Research Center of Gastroenterology and Liver Diseases, Shahid Beheshti University, M.C., Tehran, Iran
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Jafarzadeh A, Hassanshahi GH, Nemati M. Serum levels of high-sensitivity C-reactive protein (hs-CRP)in Helicobacter pylori-infected peptic ulcer patients and its association with bacterial CagA virulence factor. Dig Dis Sci 2009; 54:2612-6. [PMID: 19160050 DOI: 10.1007/s10620-008-0686-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2008] [Accepted: 12/23/2008] [Indexed: 12/13/2022]
Abstract
OBJECTIVE CRP is a marker of inflammation and infection of the gastric mucosa with Helicobacter pylori, which causes an inflammatory reaction. It has been reported that CagA(+) H. pylori strains induce more severe gastric inflammation and are also associated with higher risks of peptic ulcer and gastric cancer. The purpose of this study was to compare serum concentrations of hs-CRP in H. pylori-infected peptic ulcer (PU) patients, H. pylori infected asymptomatic (AS) carriers, and a healthy control group, and their association with bacterial virulence factor CagA. MATERIAL AND METHODS A total of 60 H. pylori infected PU patients (30 patients were positive for anti-CagA antibody and 30 were negative for anti-CagA antibody), 53 H. pylori-infected AS carriers (25 subjects were positive for anti-CagA antibody and 28 were negative for anti-CagA antibody), and 22 healthy H. pylori-negative subjects (as a control group) were enrolled in the study. Serum concentrations of hs-CRP were measured by use of an ELISA method. RESULTS The mean serum level of hs-CRP in all PU patients (124.9±32.4 μg/dl) was significantly higher than that in all AS subjects (18.6±2.6 μg/dl; P<0.001) and the healthy uninfected control group (10.7±2.9 μg/dl; P<0.0001). Moreover, the mean serum level of hs-CRP in the AS group was significantly higher than that observed in the uninfected control group (P<0.04). No significant difference was observed between mean serum levels of hs-CRP of PU patients with positive test for anti-CagA antibody (132.6±49.4 μg/dl) and PU patients with negative test for anti-CagA antibody (117.1±42.9 μg/dl). Moreover, mean serum levels of hs-CRP were similar in AS subjects with positive test for anti-CagA (18.4±3.1 μg/dl) and in those who were negative for anti-CagA antibody (18.9±4.1 μg/dl). CONCLUSION The results of this study showed that mean serum concentrations of hs-CRP in PU patients and in H. pylori infected AS carriers were higher than in a healthy control group. Although H. pylori infection is associated with higher serum levels of hs-CRP, serum concentrations of this inflammatory marker were not affected by expression of bacterial CagA virulence factor.
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Affiliation(s)
- A Jafarzadeh
- Department of Immunology, Medical School, Rafsanjan University of Medical Sciences and Health Services, Rafsanjan, Iran.
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21
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Sugimoto M, Zali MR, Yamaoka Y. The association of vacA genotypes and Helicobacter pylori-related gastroduodenal diseases in the Middle East. Eur J Clin Microbiol Infect Dis 2009; 28:1227-1236. [PMID: 19551413 PMCID: PMC3130054 DOI: 10.1007/s10096-009-0772-y] [Citation(s) in RCA: 70] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2009] [Accepted: 06/11/2009] [Indexed: 12/12/2022]
Abstract
The variations in the three regions of the Helicobacter pylori vacA gene, the signal (s1 and s2), intermediate (i1 and i2) and middle regions (m1 and m2), are known to cause the differences in vacuolating activities. However, it was unclear whether these vacA genotypes are associated with the development of gastric cancer and peptic ulcer in the Middle East. The aim was to identify the prevalence of vacA genotypes in the Middle East and the association with gastroduodenal diseases. We investigated the relationship of vacA genotypes to H. pylori-related disease development by meta-analysis using previous reports of 1,646 patients from the Middle East. The frequency of the vacA s1, m1 and i1 genotypes in the Middle Eastern strains was 71.5% (1,007/1,409), 32.8% (427/1,300) and 40.7% (59/145), respectively. Importantly, the frequency of vacA s- and m-region genotypes significantly differed between the north and south parts of the Middle East countries (P < 0.001). The vacA genotypes significantly increased the risk of gastric cancer (odds ratio [OR]: 4.02, 95% confidence interval [CI]: 1.98-8.14 for the s1 genotype; 2.50, 1.62-3.85 for m1; 5.27, 1.97-14.1 for s1m1; 15.03, 4.69-48.17 for i1) and peptic ulcers (OR: 3.07, 95% CI: 2.08-4.52 for s1; 1.81, 1.36-2.42 for m1). The cagA-positive genotype frequently coincided with the s1, m1 and i1 genotypes. The vacA s- and m-region genotypes may be useful risk factors for gastrointestinal diseases in the Middle East, similar to European and American countries. Further studies will be required to evaluate the effects of the i-region genotype.
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Affiliation(s)
- M. Sugimoto
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, 2002 Holcombe Blvd., (111D) Rm 3A-320, Houston, TX 77030, USA
| | - M. R. Zali
- Department of Internal Medicine and Gastroenterology, Research Center for Gastroenterology and Liver Disease, Shaheed Beheshti University, Tehran, Iran
| | - Y. Yamaoka
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, 2002 Holcombe Blvd., (111D) Rm 3A-320, Houston, TX 77030, USA. Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
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Jafarzadeh A, Mirzaee V, Ahmad-Beygi H, Nemati M, Rezayati MT. Association of the CagA status of Helicobacter pylori and serum levels of interleukin (IL)-17 and IL-23 in duodenal ulcer patients. J Dig Dis 2009; 10:107-12. [PMID: 19426392 DOI: 10.1111/j.1751-2980.2009.00371.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE It has been reported that the cytotoxin-associated gene A (cagA+) H. pylori strains induce severe gastric mucosal inflammation. The aim of this study was to investigate the association of the virulence factor CagA with IL-17 and IL-23 serum levels in duodenal ulcer (DU) patients and H. pylori-infected asymptomatic (AS) carriers. METHODS In total, 45 H. pylori-infected DU patients were enrolled to study: 23 tested positive for the anti-CagA antibody (anti-CagA+) and 22 tested negative for the anti-CagA antibody (anti-CagA-), 30 were AS carriers (15 were anti-CagA+ and 15 were anti-CagA-) and 15 were healthy uninfected participants (as a control group). The IL-17 and IL-23 serum levels of participants were measured by enzyme-linked immunosorbent assay method. RESULTS The mean IL-17 levels in DU patients were significantly higher than those in AS and control groups (P < 0.001 and P < 0.0001 respectively). In the DU group, the mean IL-17 levels in participants testing positive for anti-CagA (10.84 +/- 5.79 pg/mL) were significantly higher than those observed in participants testing negative for anti-CagA (7.65 +/- 4.74 pg/mL; P < 0.05). The mean IL-23 levels in the DU and AS groups were significantly higher than in the control group (P < 0.02 and P < 0.03 respectively) but were not significantly different in participants testing positive and negative for anti-CagA. CONCLUSION These results showed higher IL-17 and IL-23 serum levels in H. pylori-infected participants than in the control group. In the DU group the expression of IL-17 was influenced by the CagA factor.
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Affiliation(s)
- Abdollah Jafarzadeh
- Department of Immunology, Medical School, Rafsanjan University of Medical Sciences and Health Services, Rafsanjan, Iran.
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Rasmi Y, Sadreddini M, Jamali M, Peirouvi T, Khosravifa F. Frequency of Cytotoxin Associated Gene A(+) Helicobacter pylori in Peptic Ulcer Disease: Difference Between Gastric and Duodenal Ulcer Disease. JOURNAL OF MEDICAL SCIENCES 2009. [DOI: 10.3923/jms.2009.146.150] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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Talebkhan Y, Mohammadi M, Mohagheghi MA, Vaziri HR, Eshagh Hosseini M, Mohajerani N, Oghalaei A, Esmaeili M, Zamaninia L. cagA gene and protein status among Iranian Helicobacter pylori strains. Dig Dis Sci 2008; 53:925-32. [PMID: 17939043 DOI: 10.1007/s10620-007-9978-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2007] [Accepted: 08/15/2007] [Indexed: 12/11/2022]
Abstract
The wide geographic genetic diversity of Helicobacter pylori (Hp) and, in particular, the varying prevalence of cagA in different countries has been documented repeatedly. This study was designed to determine the frequency of cagA in Iranian Hp strains by means of genotyping and assessment of host antibodies. Helicobacter pylori strains from 235 patients, including 174 non-ulcer dyspepsia, 25 peptic ulcer and 36 gastric cancer patients, were studied. The frequencies of the 5', middle and 3' terminal regions of the cagA gene were 90.6, 57.6, 89%, respectively, with no correlation to the clinical outcomes. Antibodies against the CagA protein were present in 90.7% of patients. Multiple biopsy sampling in 97 cases revealed multiple infection in 16.5% of the patients. Sequencing of the seven variants of the 3' end of the cagA gene revealed no clustering and the distribution of the Iranian strains among those of other countries. Our results from the genotyping and serology analyses confirm that the majority of Iranian Hp strains are cagA-positive.
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Affiliation(s)
- Yeganeh Talebkhan
- Biotechnology Research Center, Pasteur Institute of Iran, Tehran 13164, Iran
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25
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Jafarzadeh A, Rezayati MT, Nemati M. Specific serum immunoglobulin G to H pylori and CagA in healthy children and adults (south-east of Iran). World J Gastroenterol 2007; 13:3117-21. [PMID: 17589930 PMCID: PMC4172621 DOI: 10.3748/wjg.v13.i22.3117] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the serologic IgG response to H pylori and CagA across age groups and in healthy children and adults.
METHODS: Totally, 386 children aged 1-15 years and 200 adults aged 20-60 years, were enrolled to study. The serum samples of participant were tested for presence of anti-H pylori and anti-CagA IgG by using ELISA method.
RESULTS: The seroprevalence of H pylori in adults was significantly higher than that observed in children (67.5% vs 46.6%; P < 0.000003). In children, the seropositivity rate in males (51.9%) was significantly (P < 0.05) higher than that observed in females (41.7%). The prevalence of serum anti-CagA antibody was 72.8% and 67.4% in infected children and adults, respectively. The mean titer of serum anti-CagA antibodies was significantly higher among children in comparison to adults (64.1 Uarb/mL vs 30.7; P < 0.03). In infected children and adults the prevalence of serum anti-CagA antibody was higher in males compared to females (78.4% vs 66.3%; P = 0.07 and 75.6% vs 54.71%; P < 0.04, respectively). The age-specific prevalence of anti-H pylori and anti-CagA antibody (in infected subjects) was 37.6% and 59.57% at age 1-5 years, 46.9% and 75% at age 6-10 years, 54.9% and 79.45% at age 11-15, 59.01% and 83.33% at age 20-30 years, 66.6% and 60.52% at age 31-40 years, 73.46% and 63.88% at age 41-50 years and 75.75% and 60% at age 51-60 years with mean titer of anti-CagA antibody of 75.94, 63.32, 57.11, 52.06, 23.62, 21.52 and 21.80 Uarb/mL, respectively. There was significant difference between mean serum anti-CagA antibody in age subgroups (P < 0.001).
CONCLUSION: These results showed that anti-H pylori and anti-CagA antibodies were common in the children and adults. The H pylori-specific antibodies influenced by age and sex of subjects. Moreover, it seems that males are more susceptible to infection with CagA+ strains compared to females. The seroprevalence of anti-CagA antibody was increased with age, up to 30 years and then decreased. It was also found that the magnitude of the IgG response to CagA decreased with advanced age.
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Affiliation(s)
- A Jafarzadeh
- Department of Immunology, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
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Hashemi MR, Rahnavardi M, Bikdeli B, Dehghani Zahedani M. H pylori infection among 1000 southern Iranian dyspeptic patients. World J Gastroenterol 2006; 12:5479-82. [PMID: 17006984 PMCID: PMC4088229 DOI: 10.3748/wjg.v12.i34.5479] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To describe the frequency of H pylori infection among 1000 southern Iranian dyspeptic patients.
METHODS: A prospective study was performed in a referral hospital in south of Iran from 1999 to 2005. One thousand dyspeptic patients (518 males, mean ± SD age of 49.12 ± 12.82 years) consecutively underwent upper gastrointestinal endoscopy. Multiple gastric antral biopsy samples were taken from all patients for rapid urease test and histopathologic examination (96.9% satisfactory samples). Patients were considered H pylori-infected if one or both tests were positive.
RESULTS: Six hundred and seventy-one patients (67.1%, 95% confidence interval [CI]: 64.2%-70.0%) were H pylori-infected. H pylori positivity was significantly more frequent in patients with peptic ulcer disease (PUD) than in those with non-ulcer dyspepsia (P < 0.001). Male-to-female ratio for duodenal and gastric ulcers was 2.7:1 and 1.5:1, respectively. Moreover, the duodenal-to-gastric ulcer ratio was 1.95:1. The frequency of H pylori infection among those with endoscopic diagnosis of gastritis, duodenal ulcer, gastric ulcer, and normal mucosa was 70.1% (398/568), 86.2% (150/174), 71.9% (64/89), and 33.5% (54/161), respectively. H pylori infection, male sex, and older age were independently associated with PUD in multivariate analysis. H pylori positivity was associated with chronic gastritis, and chronic active gastritis with odds ratios of 34.21 (95% CI: 12.19%-96.03%) and 81.21 (95% CI: 28.85%-228.55%), respectively.
CONCLUSION: H pylori and PUD are highly frequent in dyspeptic patients from south of Iran. H pylori is a cardinal risk factor for chronic active or inactive gastritis.
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Affiliation(s)
- Mahmood Reza Hashemi
- Department of Gastroenterology, Hormozgan University of Medical Sciences, Bandarabbas, Artesh University of Medical Sciences, Tehran, Iran
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