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Association of H.pylori cagA Gene with Duodenal Ulcer & Gastric Carcinoma in Bangladeshi Patients

Ritu Saha , Sharmeen Ahmed, Humayun Sattar, Maksuma Begum, Bhuiyan Mohammad Mahtab Uddin, Ahmed Abu Saleh, Ruhul Amin Miah
American Journal of Microbiological Research. 2018, 6(2), 57-62. DOI: 10.12691/ajmr-6-2-4
Published online: April 04, 2018

Abstract

Background: Prolong infection with Helicobacter pylori may lead to chronic inflammation of gastroduodenal mucosa which in turns develops into severe diseases like peptic ulcer and gastric carcinoma. Bacterial virulence factor Cytotoxin Associated gene (cagA) is found to be responsible for developing such severe diseases in different countries. So this study was conducted to assess the relationship between occurrence of several gastroduodenal diseases and the presence of H. pylori cagA gene in Bangladeshi patients. Methods: Endoscopic gastroduodenal biopsy sample of 113 dyspeptic patients from different districts of Bangladesh were studied. H. pylori infection was detected by Rapid urease test, PCR of ureC gene and histological staining (Geimsa). Gastroduodenal disease was diagnosed by histopathological examination and cagA gene was detected by PCR. Result: H. pylori infection was identified among 48% (54/113) patients. Fifty seven percent of H. pylori infected patients were found to be cagA gene positive. cagA gene is significantly associated with Duodenal ulcer (p= .024) and Gastric carcimoma (p < .001). However, a further larger study is required to confirm this finding.

1. Introduction

Helicobacter pylori is a curved Gram negative bacteria that is colonizes in the gastric mucosa of about half of the world’s population where it causes a variety of clinical outcomes ranging from asymptomatic carriage to gastritis, peptic ulcers, and cancer 1. However, less than 20% of infected patients present with clinical symptoms suggesting that, the disease severity is dependent on interactions between the host and the environment, and bacterial virulence 2.

Many putative virulence factors have been identified in H. pylori that contribute to its pathogenesis. The 128-kDa cytotoxin-associated gene encoded antigen A (cagA) and vacuolating cytotoxin antigen gene (vacA) are known as the most important ones 3, 4.

The cagA gene is a strain-specific H pylori gene and has been widely recognized as a marker for strains that confer increased risk for peptic ulcer disease 5 and gastric cancer 6. The cagA gene is present downstream of a 40-kb cluster of virulence genes known as the cag pathogenicity island (cag- PAI). These virulence genes encode a type IV secretion system that forms a syringe-like structure to translocate the cagA protein into the gastric epithelial cells. The cag-PAI has also been implicated in the induction of IL-8 in cultured gastric cells 7. This property contributes to the virulence capability of the cag positive strains by enhancing their proinflammatory power.

In contrast to the cagA gene, nearly all H. pylori strains around the world has possesed the vacA gene 8. A strong correlation has been found between the presence of the cagA gene with expression of the vacuolating cytotoxin activity 9. Furthermore, it has been found that most strains possessing cagA also possess the more virulent vacuolating form of VacA 10.

A number of recent studies have suggested that, infection with cag PAI-positive strains of H. pylori may significantly increase the risk of developing severe gastric mucosal inflammation, duodenal ulceration and gastric cancer and its precursor lesions 11, 12.

Although, serological methods to detect specific antibodies to the H. pylori cagA protein would be more suitable 13 than genotype identification as it needs endoscopic gastroduodenal biopsy samples, Genotype identification is more accurate procedure as subjects infected with H. pylori strains containing the cagA gene do not always induce serum cagA antibody 14. Moreover, it has been suggested that host immunological responses to H. pylori may vary in different populations 15.

H. pylori has a global distribution but geographical differences in the prevalence of cagA status among H. pylori isolates have been reported 16. Even within country, the prevalence rate may vary between distinct geographic region 17. Moreover no study was done to determine the association between cagA gene and gastroduodenal diseases in our country.

So the aim of this study was to determine the association between the presence of cagA genotype in H. pylori and the severity of different gastroduodenal diseases in a group of Bangladeshi patients.

2. Methods

The study was conducted in Department of Microbiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka.

2.1. Patients and Gastric Biopsy Samples

The present study included 113 Bangladeshi patients who underwent upper Gastrointestinal endoscopic examination at outpatient department of Department of Gastroenterology of Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbagh, Dhaka, and Dhaka Medical college Hospital, Dhaka between March, 2015 to February 2016. Out of 113 patients 65 patients were endoscopically reported as gastritis followed by 18 duodenal ulcer, 17 gastric ulcer and 13 gastric carcinoma. Patient aged from 18 to onward presenting with symptoms of dyspepsia more than 1 month were included in the study. Patients who received H. pylori eradication treatment in the previous 2 months 18, Elderly individuals who had age more than 65 years, had severe medical or surgical illnesses or had used proton pump inhibitors, nonsteroidal anti-inflammatory drugs, colloidal bismuth compounds, or antibiotics within 4 weeks of enrollment were excluded from the study 19.

The study populations were categorized into 2 groups based on the case definition used in this study: H. pylori positive patients (n = 54) & H. pylori negative patients (n = 59). Patients were considered as H. pylori positive when positive results were obtained in at least two of the three tested methods (Rapid urease test, histology for H. pylori and PCR for ureC gene) and considered as negative when the results of all diagnostic tests were negative. Gastroduodenal diseases was diagnosed by endoscopic and histopathological examinations and established in accordance with the Sydney System Classification.

From each patient three pieces of gastric tissue were taken from nonlesional mucosa of the lesser curvature side of the antrum and three pieces from midbody for H. pylori detection (Pentax Video-Endoscopy EG/3485). Additional biopsies were taken from margins of malignant looking ulcers or proliferative growths for histopathological examination to confirm the diagnosis. Two specimen, each from the antrum and body were fixed in 10% buffered formalin and send to the Pathology Department of BSMMU and DMC hospital for histopathological examination. One specimen each from the body and antrum were examined for the presence of H. pylori by rapid urease test and one specimen from the antrum and body were preserved in 1.5 ml microcentrifuge tube containing 1 ml phosphate buffer solution for detection of H. pylori ureC gene and cagA gene by PCR. All biopsy samples were stored at -20°C until DNA extraction from the samples were performed.

2.2. DNA Extraction and PCR for ureC and cagA Gene

DNA from gastric tissues was extracted by using the QlAamp (QIAGENÒ) DNA Mini Kit according to the manufecturer’s instructions. For confirming the presence of H. pylori DNA in tissue, the ureC gene was identified by PCR using the following primers 20. (Figure 1)

H. pylori cagA gene was detected by using following primers designed by Yamaoka et al. (1997) 21 (Figure 2).

The PCR was performed as previously reported in another study 22. The DNA were denatured at 94°C for 4 minutes, followed by 35 cycles at 94°C for 30 seconds, 60°C for 30 seconds, and 72°C for 30 seconds with a final extension at 72°C for 7 minutes.

This work was ethically approved by Institutional Review Board, BSMMU; process number BSMMU/2015/10008. Written, informed consent was obtained from all patients.

2.3. Statistical Analysis

The sample size was calculated by using the following formula. A 95% confidence interval was used. The seroprevalence of H. pylori infection in Bangladesh was 92% and acceptable error was 5%. The statistical analysis was based on the creation and categorization of variables and was performed by using SPSS version 20.0 (Statistical Program for the Social Sciences Inc., Chicago, USA). The Chi-square test or Fisher’s exact test were used to compare between proportions. Values of p < 0.05 were considered statistically significant.

3. Results

The Out of 113 patients, majority (65) were endoscopically reported as gastritis followed by 18 duodenal ulcer, 17 gastric ulcer and 13 gastric carcinoma. The study populations were between the ages 18- 65 years, with mean age 39.4±12.8 years. Majority of gastritis patients (15, 23%) were in age group between 21-30 years whereas 35.3% (6/17) of gastric ulcers and 46.2 % (6/13) of gastric carcinoma patients were in 41-50 years of age group. Thirty three percent (6/18) patients of duodenal ulcer were in age group between 60-65 years (Table 1). 72 (63.7%) of the study population were male and 41 (36.3%) were female with male female ratio of being 2:1. The relation between endoscopic findings and histopathologial findings are shown in Table 2. Endoscopic findings of the study population were significantly associated with histopathological findings (p<.001) (Table 2). In the present study 47.8% (54/113) were defined as H. pylori positive cases and 52.2 % (59/113) were considered as H. Pylori negative cases (Table 3).

The rate of H. pylori infection in different histopathologically confirmed gastroduodenal diseases are demonstrated in Table-4. Gastric carcinoma is significantly associated with H. pylori infection (p=.046). Table-5 has revealed the frequency of positive cagA gene in different gastroduodenal diseases among H. pylori positive cases. Out of 54 H. pylori positive patients, 31 (57.4%) were cagA gene positive.

The cagA gene is significantly associated with duodenal ulcer cases (p=.024) and gastric carcinoma (p=<.001).

4. Discussion

In the present study 47.8% was diagnosed as H. pylori positive cases but the prevalence of H. pylori in Bangladesh is reported to be 42% by 2 years of age with a rapid increase to 67% by 10 years of age 23. On the other hand, Rahman et al. (2009) 24 has found H. pylori positive in 53.3% cases by RUT and in 43.4% cases by histology. In another study about 92% adult population in Bangladesh was seropositive for H. pylori 25. The present study has found lower H. pylori detection rate in comparison to a study done by Hanif et al. (2010) 26 in Pakistan who found 68% H. pylori positive by RUT, 62% by PCR for ureC gene and 64% by histological staining. On the other hand, 91% of the studied dyspeptic patients were positive for H. pylori in an Egyptian study by Amer et al. 27 Prevalence of H. pylori infection varies between and within countries depending on socioeconomic factors, different demographic distribution of the organism among various regions, previous antibiotic consumption 28, 29 and the method of detection of infection because gastroduodenal biopsy based tests may give false negative results due to sampling error 30

Among the histopathology confirmed intestinal metaplasia patients, 75% were H. pylori positive cases but In the current study, 39.3% of the gastritis and 58.8% of the duodenal ulcer patients were infected with H. pylori. This findings correlate with the findings reported by Helaly et al. (2009) 31 in Egypt who found 41.1% of the gastritis patients and 54.5% of duodenal ulcer patients to be H. pylori positive. In spite of high prevalence rate of H. pylori infection among dyspeptic patients, a low incidence of gastric adenocarcinoma has been found in the present study as reported by Miwa et al, 2002 32.

In the present study, H. pylori infection was predominant among the gastric carcinoma patients (p=.046). Yamagata et al. (2000) 33 in Japan observed similar findings among the age-adjusted gastric cancer patients. Only a minority of infected patients develops severe diseases and variations in clinical outcome may be due to the considerable genetic diversity of the H. pylori strains that cause infection, and host factors.

The prevalence of cagA positive H. pylori varies among different geographic regions. The primary geographic influence has an important role in the adaptation of organism to the environment and climatc conditions 34. In this study, out of 54 H. pylori positive cases 31(57.4%) were cagA gene positive. This finding correlates with the findings of several studies, where cagA positivity rate was reported 61% in China 35, 61.6% in Tunissia 36 and 65.9% in Brazil 37. Almost similar finding was reported by Rahman et al. 38 (2003) in Bangladesh who found 68.4% cagA gene positive among 57 culture positive H. pylori cases. H. pylori cagA positive strains are more virulent causing higher level of gastric mucosal inflammation in gastritis and gastric cancer 39. In the present study, in relation to different gastroduodenal diseases cagA gene was positive in 70% of duodenal ulcer and 41.7% of gastritis patients. It has been reported that, cagA was present among 75% of the strains from the patients with duodenal ulcer disease and 55% of strains from patients with gastritis in Bangladeshi patients 38. The cagA was significantly associated with duodenal ulcer cases (p =.024) in this study. This finding is in agreement with studies done by Nomura et al. (2002) 5 and Yamoka et al. (1999) 40 in Japan who found strong association between cagA gene and peptic ulcer diseases but in contrast, no association was found between cagA status and duodenal ulcer in Singapore 41. The large variation in the H. pylori genome that amplifies the cagA gene from H. pylori isolated in one country failed to detect cagA from another country 42. Moreover, there may be several distinct form of cagA gene with an uneven geographical distribution that may provide a marker for difference in virulence among cagA positive H. pylori strain. This may be the reason for difference in cagA status in different countries. Moreover, selection criteria of patients and large diverse study groups with respect to genotypes and clinical symptoms are also considered as important factor for variation in results in different regions 43

A high frequency of cagA-positive strains was observed in intestinal metaplasia and gastric dysplasia patients (Table 5), indicating that a statistical association could be reached by increasing the number of patients in future studies.

In this study, 87.5% (7/8) of the gastric carcinoma patients were infected with cagA gene positive strains. Zohu et al (2004) 44 reported 100% of gastric carcinoma patients were cagA positive. A significant association is observed between cagA status and gastric carcinoma (p <.001) in the present study. It has been suggested that, the persons infected with cagA positive H. pylori are at considerably increased risk of gastric cancer than with uninfected subjects 45.

5. Conclusion

Our present study demonstrated that, the cagA gene is significantly associated with duodenal ulcer disease and gastric carcinoma in Bangladeshi patients. One of the major limitations of our study was that we could not compare our result with serological test as anti cagA antibody cannot be detected due to limitation of time and budget. Besides H. pylori colonizer was not identified as asymptomatic patients were not included in the study. Though our study provides a significant association between infections by cagA gene-positive strains of H. pylori and severe clinical outcomes, but future multicentre studies on a large scale with a full characterization of Bangladeshi H pylori isolates are required to confirm our findings and overcome above mentioned limitations.

Acknowledgements

We are very grateful to Scientific Officer Md. Yunus Ali & all the laboratory technologists of Department of Microbiology, BSMMU.

References

[1]  Atherton J. (2006). The pathogenesis of H pylori-induced gastro-duodenal diseases. Annu. Rev. Pathol;1: 63-96.
In article      View Article  PubMed
 
[2]  Kamali-Sarvestani E, Bazargani A, Masoudian, Lankarani K, Taghavi AR, Saberifiroozi M (2006). Association of H. pylori cagA and vacA Genotypes and IL-8 Gene Polymorphisms with Clinical Outcome of Infection in Iranian Patients with Gastrointestinal Diseases, World Journal of Gastroenterology ; 12 (32): 5205-5210.
In article      PubMed  PubMed
 
[3]  Graham DY & Yamaoka Y (1998). H. pylori and cagA: relationships with gastric cancer, duodenal ulcer, and reflux esophagitis and its complications, Helicobacter; 3: 145-151.
In article      View Article  PubMed
 
[4]  Atherton JC, Cover TL, Twells RJ, Morales MR, Hawkey CJ, Blaser MJ (1999). Simple and accurate PCR-based system for typing vacuolating cytotoxin alleles of Helicobacter pylori, Journal of Clinical Microbiology; 37: 2979-2982.
In article      PubMed  PubMed
 
[5]  Nomura AM, Perez-Perez GI, Lee J, Stemmermann G, Blaser MJ (2002). Relation between Helicobacter pylori cagA status and risk of peptic ulcer disease. American Journal of Epidemiology; 155: 1054-1059.
In article      View Article  PubMed
 
[6]  Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH et al. (1995). Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach, Cancer Research; 55: 2111-2115.
In article      PubMed
 
[7]  Fischer W, Püls J, Buhrdorf R, Gebert B, Odenbreit S, Haas R (2001). Systematic mutagenesis of the Helicobacter pylori cag pathogenicity island: essential genes for CagA translocation in host cells and induction of interleukin-8, Molecular Microbiology; 42: 1337-1348.
In article      View Article  PubMed
 
[8]  Chen XJ, Yan J, Shen YF. (2005). Dominant CagA/VacA genotypes and coinfection frequency of H. pylori in peptic ulcer or chronic gastritis patients in Zhejiang Province and correlations among different genotypes, coinfection and severity of the diseases. Chin. Med. J. Engl. 118: 460-467.
In article      PubMed
 
[9]  Sharma S, Tynnyry M, Miller G. (1995). Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro. Infect. Immunol. 63: 1681-1687.
In article      PubMed  PubMed
 
[10]  Argent RH, Thomas RJ, Letley DP, Ritting MG, Hardie KR, Atherton JC. 2008. Functional association between the Helicobacter pylori virulence factors VacA and CagA. J. Med. Microbiol. 57: 145-150.
In article      View Article  PubMed
 
[11]  Essa AS, Nouh MA, Ghaniam NM, et al. (2008). Prevalence of cagA in relation to clinical presentation of Helicobacter pylori infec¬tion in Egypt. Scand J Infect Dis; 40: 730-733.
In article      View Article  PubMed
 
[12]  Destura RV, Labio ED, Barrett LJ, et al. (2004). Laboratory diagnosis and susceptibility profile of Helicobacter pylori infection in the Philippines; Ann Clin Microbiol Antimicrob; 3: 25-30
In article      View Article  PubMed
 
[13]  Figueiredo C, Quint W, Nouhan N, van den Munckhof H, Herbrink P, Scherpenisse J, et al. (2001). Assessment of Helicobacter pylori vacA and cagA genotypes and host serological response. J. Clin. Microbiol. 39: 1339-1344.
In article      View Article  PubMed
 
[14]  Shiota S, Matsunari O, Watada M, Yamaoka Y. (2010). Serum Helicobacter pylori CagA antibody as a biomarker for gastric cancer in east-Asian countries. Future Microbiol. 5: 1885-1893.
In article      View Article  PubMed
 
[15]  Saverymuttu S. (2001). Genetic diversity in the Helicobacter pylori cag pathogenicity island and effect on expression of anti-CagA serum antibody in UK patients with dyspepsia. J. Clin. Pathol. 54: 219-223.
In article      View Article  PubMed
 
[16]  Saber T,. Ghonaim MM, Yousef AR, Khalifa A, Qurashi HA, Shaqhan M et al. (2015) Association of Helicobacter pylori cagA Gene with Gastric Cancer and Peptic Ulcer in Saudi Patients, J. Microbiol. Biotechnol., 25(7): 1146-1153.
In article      View Article  PubMed
 
[17]  Fock KM and Ang TL (2010). Epidemiology of Helicobacter pylori Infection and Gastric Cancer in Asia, Journal of Gastroenterology and Hepatology; 25 (3): 479-486.
In article      View Article  PubMed
 
[18]  Ye BD, Kim SG, Park JH, Kim JS, Jung HC, Song IS. (2009) The interleukin-8-251 A allele is associated with increased risk of noncardia gastric adenocarcinoma in Helicobacter pylori infected Koreans, J Clin Gastroenterol, 43, 233e9.
In article      
 
[19]  Tongtawee T, Kaewpitoon S, Kaewpitoon N, Dechsukhum C, Loyd RA, Matrakool L, (2015) .Correlation between Gastric Mucosal Morphologic Patterns and Histopathological Severity of Helicobacter pylori Associated Gastritis Using Conventional Narrow Band Imaging Gastroscopy, Biomedical Research International :1-7.
In article      View Article  PubMed
 
[20]  Lu JJ, Perng CL, Shyu RY, Chen CH, Lou Q, Chong KF et al. (1999).Comparison of Five PCR Methods for Detection of Helicobacter pylori DNA in Gastric Tissues, Journal of Clinical Microbiology; 37 (3): 772-774.
In article      PubMed  PubMed
 
[21]  Yamaoka Y, Kita M, Kodama T, Sawai N, Kashima K, and Imanishi J (1997). Induction of Various Cytokines and Development of Severe Mucosal Inflammation by cagA Gene Positive Helicobacter pylori Strains, Gut; 41 (4): 442-451.
In article      View Article  PubMed
 
[22]  Taguchi A, Ohmiya N, Shirai K, Mabuchi N, Itoh A, Hirooka Y, Niwa Y, Goto H, (2005). Interleukin-8 promoter polymorphism increases the risk of atrophic gastritis and gastric cancer in Japan; Cancer Epidemiol Biomarkers Prev, 14: 2487-2493.
In article      View Article  PubMed
 
[23]  Clemens J, Albert MJ, Rao M, Huda S, Qadri F, Van Loon FP et al. (1996). Sociodemographic, Hygienic and Nutritional Correlates Helicobacter Pylori Infection of Young Bangladeshi Children, Pediatric Infectious Disease Journal; 15 (12): 1113-1118.
In article      View Article  PubMed
 
[24]  Rahman SH, Rahman MA, Arfin MS, Alam MM, Bhuiyan TM, Ahmed N et al. (2009). Helicobacter pylori Infection and Strain Types in Adult Dyspeptic Patients Undergoing Endoscopy in a Specialized Hospital of Dhaka City, Bangladesh Journal of Medical Microbiology; 3(1): 4-9.
In article      View Article
 
[25]  Ahmad MM, Rahman M, Rumi AK, Islam S, and Hug.F, Chowdhury MF et al. (1997). Prevalence of Helicobacter pylori in asymptotic populatio -a pilot serological sudy, Bangladesh Journal of Epidemiology; 7 (4): 251-254.
In article      View Article  PubMed
 
[26]  Hanif M, Zaidi P, Rasool A, Hameedl A, Ahmed L (2010). Cytotoxin genes of Helicobacter pylori in gastroduodenal disease patients of Karachi, Asia-Pacific Journal of Molecular Biology and Biotechnology; 18(3): 333-340.
In article      
 
[27]  Amer FA, El-Sokkary RH, Elahmady M, Gheith T, Abdelbary EH, Elnagar Y et al. (2013). Helicobacter pylori genotypes among patients in a university hospital in Egypt: identifying the determinants of disease severity; Journal of Microbiology and Infectious Diseases ; 3 (3): 109-115.
In article      View Article
 
[28]  Bazzoli M, Al-Qurain A, Al-Quorain A. (1999). Campylobacter pylori in Saudi Arabia under upper gastrointestinal endoscopy. Saudi Med. J. 8: 516-518.
In article      
 
[29]  Cabrita J, Oleastro M, Matos R, Manhente A, Cabral J, Barros R, et al. (2000). Features and trends in Helicobacter pylori antibiotic resistance in Lisbon area, Portugal 1990- 1999. J. Antimicrob. Chemother. 46: 1029-1031.
In article      View Article  PubMed
 
[30]  Perez‐Perez GI, Rothenbacher D, Brenner H (2004). Epidemiology of Helicobacter pylori infection. Helicobacter; 9(s1): 1-6
In article      View Article
 
[31]  Helaly GF1, El-Afandy NM, Hassan AA, Dowidar NL, Sharaf SM Diagnostic Value of Housekeeping [glmM] GeneExpression in Antral Biopsies in Comparison to Rapid Urease Test and Histological Detection of Helicobacter Pylori Infection Egyptian Journal of Medical Microbiology, October 2009 Vol. 18, No. 4.
In article      
 
[32]  Miwa H, Go MF, Sato NH (2002). H. pylori and gastric cancer: the Asian enigma, The American journal of gastroenterology; 97(5): 1106-1112.
In article      View Article  PubMed
 
[33]  Yamagata H, Kiyohara Y, Aoyagi K, Kato I, Iwamoto H, Nakayama K et al. (2000). Impact of Helicobacter pylori Infection on Gastric Cancer Incidence in a General Japanese Population, Archives of Internal Medicine; 160(13): 1962-1962.
In article      View Article  PubMed
 
[34]  Benenson S, Halle D, Rudensky B, Faber J, Schlesinger Y, Branski D et al. (2002). Helicobacter pylori genotypes in Israeli children: the significance of geography, Journal of pediatric gastroenterology and nutrition; 35(5): 680-684.
In article      View Article  PubMed
 
[35]  Aziz F, Chen X, Yang X, Yan Q (2014). Prevalence and correlation with clinical diseases of Helicobacter pylori cagA and vacA genotype among gastric patients from Northeast China. BioMedical research international; 2014: Article ID 142980.
In article      View Article
 
[36]  Hussein NR, Mohammadi M, Talebkhan Y, Doraghi M, Letley DP, Muhammad MK (2008). Differences in virulence markers between Helicobacter pylori strains from Iraq and those from Iran: potential importance of regional differences in H. pylori-associated disease, Journal of clinical microbiology; 46(5): 1774-1779.
In article      View Article  PubMed
 
[37]  Essawi T, Hammoudeh W, Sabri I, Sweidan W, Farraj MA (2013). Determination of Helicobacter pylori virulence genes in gastric biopsies by PCR. ISRN gastroenterology, Article ID 606258: 1-4.
In article      
 
[38]  Rahman M, Mukhopadhyay AK, Nahar S, Datta S, Ahmad MM, Sarker S et al. (2003). DNA-level characterization of Helicobacter pylori strains from patients with overt disease and with benign infections in Bangladesh, Journal of clinical microbiology; 41(5): 2008-2014.
In article      View Article  PubMed
 
[39]  Hatakeyama M & Higashi H (2005). Helicobacter pylori CagA: a new paradigm for bacterial carcinogenesis, Cancer science; 96 (12): 835-843.
In article      View Article  PubMed
 
[40]  Yamaoka Y, Kodama T, Kita M, Imanishi J, Kashima K, Graham DY (1999). Relation between clinical presentation, Helicobacter pylori density, interleukin 1beta and 8 production, and cagA status, Gut; 45: 804-811.
In article      View Article  PubMed
 
[41]  Zheng PY, Hua J, Yeoh KG, Ho B (2000). Association of peptic ulcer with increased expression of Lewis antigens but not cagA, iceA, and vacA in Helicobacter pylori isolates in an Asian population, Gut; 47(1): 18-22.
In article      View Article  PubMed
 
[42]  Miehlke S, Kibler K, Kim JG, Figura N, Small SM, Graham DY et al. (1996). Allelic variation in the cagA gene of Helicobacter pylori obtained from Korea compared to the United States, American Journal of Gastroenterology, 91(7).
In article      PubMed
 
[43]  Ghotaslou R, Milani M, Akhi MT, Nahaei MR, Hasani A, Hejazi MS, Meshkini M. (2013). Diversity of Helicobacter pylori cagA and vacA genes and its relationship with clinical outcomes in Azerbaijan, Iran. Adv. Pharmaceut. Bull. 3: 57-62.
In article      PubMed  PubMed
 
[44]  Zhou J, Zhang J, Xu C and He L. (2004), cagA pylori genotype and variants in Chinese Helicobacter pylori strains and relationship to gastroduodenal diseases. Journal of Medical Microbiology, 53: 231-235.
In article      View Article  PubMed
 
[45]  Parsonnet J, Replogle M, Yang S, Hiatt R (1997). Seroprevalence of CagA-Positive Strains among Helicobacter pylori-Infected, Healthy Young Adults. Journal of Infectious Diseases, 175 (5): 1240-1242.
In article      View Article  PubMed
 

Published with license by Science and Education Publishing, Copyright © 2018 Ritu Saha, Sharmeen Ahmed, Humayun Sattar, Maksuma Begum, Bhuiyan Mohammad Mahtab Uddin, Ahmed Abu Saleh and Ruhul Amin Miah

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Cite this article:

Normal Style
Ritu Saha, Sharmeen Ahmed, Humayun Sattar, Maksuma Begum, Bhuiyan Mohammad Mahtab Uddin, Ahmed Abu Saleh, Ruhul Amin Miah. Association of H.pylori cagA Gene with Duodenal Ulcer & Gastric Carcinoma in Bangladeshi Patients. American Journal of Microbiological Research. Vol. 6, No. 2, 2018, pp 57-62. http://pubs.sciepub.com/ajmr/6/2/4
MLA Style
Saha, Ritu, et al. "Association of H.pylori cagA Gene with Duodenal Ulcer & Gastric Carcinoma in Bangladeshi Patients." American Journal of Microbiological Research 6.2 (2018): 57-62.
APA Style
Saha, R. , Ahmed, S. , Sattar, H. , Begum, M. , Uddin, B. M. M. , Saleh, A. A. , & Miah, R. A. (2018). Association of H.pylori cagA Gene with Duodenal Ulcer & Gastric Carcinoma in Bangladeshi Patients. American Journal of Microbiological Research, 6(2), 57-62.
Chicago Style
Saha, Ritu, Sharmeen Ahmed, Humayun Sattar, Maksuma Begum, Bhuiyan Mohammad Mahtab Uddin, Ahmed Abu Saleh, and Ruhul Amin Miah. "Association of H.pylori cagA Gene with Duodenal Ulcer & Gastric Carcinoma in Bangladeshi Patients." American Journal of Microbiological Research 6, no. 2 (2018): 57-62.
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  • Table 2. Relation between Endoscopic findings and histopathological findings among study population (N =113)
  • Table 4. Rate of H. pylori infection in different gastrointestinal diseases confirmed by histopathology (n=113)
  • Table 5. Frequency of positive cagA gene in different gastroduodenal diseases among H. pylori positive cases (N =54)
[1]  Atherton J. (2006). The pathogenesis of H pylori-induced gastro-duodenal diseases. Annu. Rev. Pathol;1: 63-96.
In article      View Article  PubMed
 
[2]  Kamali-Sarvestani E, Bazargani A, Masoudian, Lankarani K, Taghavi AR, Saberifiroozi M (2006). Association of H. pylori cagA and vacA Genotypes and IL-8 Gene Polymorphisms with Clinical Outcome of Infection in Iranian Patients with Gastrointestinal Diseases, World Journal of Gastroenterology ; 12 (32): 5205-5210.
In article      PubMed  PubMed
 
[3]  Graham DY & Yamaoka Y (1998). H. pylori and cagA: relationships with gastric cancer, duodenal ulcer, and reflux esophagitis and its complications, Helicobacter; 3: 145-151.
In article      View Article  PubMed
 
[4]  Atherton JC, Cover TL, Twells RJ, Morales MR, Hawkey CJ, Blaser MJ (1999). Simple and accurate PCR-based system for typing vacuolating cytotoxin alleles of Helicobacter pylori, Journal of Clinical Microbiology; 37: 2979-2982.
In article      PubMed  PubMed
 
[5]  Nomura AM, Perez-Perez GI, Lee J, Stemmermann G, Blaser MJ (2002). Relation between Helicobacter pylori cagA status and risk of peptic ulcer disease. American Journal of Epidemiology; 155: 1054-1059.
In article      View Article  PubMed
 
[6]  Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH et al. (1995). Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach, Cancer Research; 55: 2111-2115.
In article      PubMed
 
[7]  Fischer W, Püls J, Buhrdorf R, Gebert B, Odenbreit S, Haas R (2001). Systematic mutagenesis of the Helicobacter pylori cag pathogenicity island: essential genes for CagA translocation in host cells and induction of interleukin-8, Molecular Microbiology; 42: 1337-1348.
In article      View Article  PubMed
 
[8]  Chen XJ, Yan J, Shen YF. (2005). Dominant CagA/VacA genotypes and coinfection frequency of H. pylori in peptic ulcer or chronic gastritis patients in Zhejiang Province and correlations among different genotypes, coinfection and severity of the diseases. Chin. Med. J. Engl. 118: 460-467.
In article      PubMed
 
[9]  Sharma S, Tynnyry M, Miller G. (1995). Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro. Infect. Immunol. 63: 1681-1687.
In article      PubMed  PubMed
 
[10]  Argent RH, Thomas RJ, Letley DP, Ritting MG, Hardie KR, Atherton JC. 2008. Functional association between the Helicobacter pylori virulence factors VacA and CagA. J. Med. Microbiol. 57: 145-150.
In article      View Article  PubMed
 
[11]  Essa AS, Nouh MA, Ghaniam NM, et al. (2008). Prevalence of cagA in relation to clinical presentation of Helicobacter pylori infec¬tion in Egypt. Scand J Infect Dis; 40: 730-733.
In article      View Article  PubMed
 
[12]  Destura RV, Labio ED, Barrett LJ, et al. (2004). Laboratory diagnosis and susceptibility profile of Helicobacter pylori infection in the Philippines; Ann Clin Microbiol Antimicrob; 3: 25-30
In article      View Article  PubMed
 
[13]  Figueiredo C, Quint W, Nouhan N, van den Munckhof H, Herbrink P, Scherpenisse J, et al. (2001). Assessment of Helicobacter pylori vacA and cagA genotypes and host serological response. J. Clin. Microbiol. 39: 1339-1344.
In article      View Article  PubMed
 
[14]  Shiota S, Matsunari O, Watada M, Yamaoka Y. (2010). Serum Helicobacter pylori CagA antibody as a biomarker for gastric cancer in east-Asian countries. Future Microbiol. 5: 1885-1893.
In article      View Article  PubMed
 
[15]  Saverymuttu S. (2001). Genetic diversity in the Helicobacter pylori cag pathogenicity island and effect on expression of anti-CagA serum antibody in UK patients with dyspepsia. J. Clin. Pathol. 54: 219-223.
In article      View Article  PubMed
 
[16]  Saber T,. Ghonaim MM, Yousef AR, Khalifa A, Qurashi HA, Shaqhan M et al. (2015) Association of Helicobacter pylori cagA Gene with Gastric Cancer and Peptic Ulcer in Saudi Patients, J. Microbiol. Biotechnol., 25(7): 1146-1153.
In article      View Article  PubMed
 
[17]  Fock KM and Ang TL (2010). Epidemiology of Helicobacter pylori Infection and Gastric Cancer in Asia, Journal of Gastroenterology and Hepatology; 25 (3): 479-486.
In article      View Article  PubMed
 
[18]  Ye BD, Kim SG, Park JH, Kim JS, Jung HC, Song IS. (2009) The interleukin-8-251 A allele is associated with increased risk of noncardia gastric adenocarcinoma in Helicobacter pylori infected Koreans, J Clin Gastroenterol, 43, 233e9.
In article      
 
[19]  Tongtawee T, Kaewpitoon S, Kaewpitoon N, Dechsukhum C, Loyd RA, Matrakool L, (2015) .Correlation between Gastric Mucosal Morphologic Patterns and Histopathological Severity of Helicobacter pylori Associated Gastritis Using Conventional Narrow Band Imaging Gastroscopy, Biomedical Research International :1-7.
In article      View Article  PubMed
 
[20]  Lu JJ, Perng CL, Shyu RY, Chen CH, Lou Q, Chong KF et al. (1999).Comparison of Five PCR Methods for Detection of Helicobacter pylori DNA in Gastric Tissues, Journal of Clinical Microbiology; 37 (3): 772-774.
In article      PubMed  PubMed
 
[21]  Yamaoka Y, Kita M, Kodama T, Sawai N, Kashima K, and Imanishi J (1997). Induction of Various Cytokines and Development of Severe Mucosal Inflammation by cagA Gene Positive Helicobacter pylori Strains, Gut; 41 (4): 442-451.
In article      View Article  PubMed
 
[22]  Taguchi A, Ohmiya N, Shirai K, Mabuchi N, Itoh A, Hirooka Y, Niwa Y, Goto H, (2005). Interleukin-8 promoter polymorphism increases the risk of atrophic gastritis and gastric cancer in Japan; Cancer Epidemiol Biomarkers Prev, 14: 2487-2493.
In article      View Article  PubMed
 
[23]  Clemens J, Albert MJ, Rao M, Huda S, Qadri F, Van Loon FP et al. (1996). Sociodemographic, Hygienic and Nutritional Correlates Helicobacter Pylori Infection of Young Bangladeshi Children, Pediatric Infectious Disease Journal; 15 (12): 1113-1118.
In article      View Article  PubMed
 
[24]  Rahman SH, Rahman MA, Arfin MS, Alam MM, Bhuiyan TM, Ahmed N et al. (2009). Helicobacter pylori Infection and Strain Types in Adult Dyspeptic Patients Undergoing Endoscopy in a Specialized Hospital of Dhaka City, Bangladesh Journal of Medical Microbiology; 3(1): 4-9.
In article      View Article
 
[25]  Ahmad MM, Rahman M, Rumi AK, Islam S, and Hug.F, Chowdhury MF et al. (1997). Prevalence of Helicobacter pylori in asymptotic populatio -a pilot serological sudy, Bangladesh Journal of Epidemiology; 7 (4): 251-254.
In article      View Article  PubMed
 
[26]  Hanif M, Zaidi P, Rasool A, Hameedl A, Ahmed L (2010). Cytotoxin genes of Helicobacter pylori in gastroduodenal disease patients of Karachi, Asia-Pacific Journal of Molecular Biology and Biotechnology; 18(3): 333-340.
In article      
 
[27]  Amer FA, El-Sokkary RH, Elahmady M, Gheith T, Abdelbary EH, Elnagar Y et al. (2013). Helicobacter pylori genotypes among patients in a university hospital in Egypt: identifying the determinants of disease severity; Journal of Microbiology and Infectious Diseases ; 3 (3): 109-115.
In article      View Article
 
[28]  Bazzoli M, Al-Qurain A, Al-Quorain A. (1999). Campylobacter pylori in Saudi Arabia under upper gastrointestinal endoscopy. Saudi Med. J. 8: 516-518.
In article      
 
[29]  Cabrita J, Oleastro M, Matos R, Manhente A, Cabral J, Barros R, et al. (2000). Features and trends in Helicobacter pylori antibiotic resistance in Lisbon area, Portugal 1990- 1999. J. Antimicrob. Chemother. 46: 1029-1031.
In article      View Article  PubMed
 
[30]  Perez‐Perez GI, Rothenbacher D, Brenner H (2004). Epidemiology of Helicobacter pylori infection. Helicobacter; 9(s1): 1-6
In article      View Article
 
[31]  Helaly GF1, El-Afandy NM, Hassan AA, Dowidar NL, Sharaf SM Diagnostic Value of Housekeeping [glmM] GeneExpression in Antral Biopsies in Comparison to Rapid Urease Test and Histological Detection of Helicobacter Pylori Infection Egyptian Journal of Medical Microbiology, October 2009 Vol. 18, No. 4.
In article      
 
[32]  Miwa H, Go MF, Sato NH (2002). H. pylori and gastric cancer: the Asian enigma, The American journal of gastroenterology; 97(5): 1106-1112.
In article      View Article  PubMed
 
[33]  Yamagata H, Kiyohara Y, Aoyagi K, Kato I, Iwamoto H, Nakayama K et al. (2000). Impact of Helicobacter pylori Infection on Gastric Cancer Incidence in a General Japanese Population, Archives of Internal Medicine; 160(13): 1962-1962.
In article      View Article  PubMed
 
[34]  Benenson S, Halle D, Rudensky B, Faber J, Schlesinger Y, Branski D et al. (2002). Helicobacter pylori genotypes in Israeli children: the significance of geography, Journal of pediatric gastroenterology and nutrition; 35(5): 680-684.
In article      View Article  PubMed
 
[35]  Aziz F, Chen X, Yang X, Yan Q (2014). Prevalence and correlation with clinical diseases of Helicobacter pylori cagA and vacA genotype among gastric patients from Northeast China. BioMedical research international; 2014: Article ID 142980.
In article      View Article
 
[36]  Hussein NR, Mohammadi M, Talebkhan Y, Doraghi M, Letley DP, Muhammad MK (2008). Differences in virulence markers between Helicobacter pylori strains from Iraq and those from Iran: potential importance of regional differences in H. pylori-associated disease, Journal of clinical microbiology; 46(5): 1774-1779.
In article      View Article  PubMed
 
[37]  Essawi T, Hammoudeh W, Sabri I, Sweidan W, Farraj MA (2013). Determination of Helicobacter pylori virulence genes in gastric biopsies by PCR. ISRN gastroenterology, Article ID 606258: 1-4.
In article      
 
[38]  Rahman M, Mukhopadhyay AK, Nahar S, Datta S, Ahmad MM, Sarker S et al. (2003). DNA-level characterization of Helicobacter pylori strains from patients with overt disease and with benign infections in Bangladesh, Journal of clinical microbiology; 41(5): 2008-2014.
In article      View Article  PubMed
 
[39]  Hatakeyama M & Higashi H (2005). Helicobacter pylori CagA: a new paradigm for bacterial carcinogenesis, Cancer science; 96 (12): 835-843.
In article      View Article  PubMed
 
[40]  Yamaoka Y, Kodama T, Kita M, Imanishi J, Kashima K, Graham DY (1999). Relation between clinical presentation, Helicobacter pylori density, interleukin 1beta and 8 production, and cagA status, Gut; 45: 804-811.
In article      View Article  PubMed
 
[41]  Zheng PY, Hua J, Yeoh KG, Ho B (2000). Association of peptic ulcer with increased expression of Lewis antigens but not cagA, iceA, and vacA in Helicobacter pylori isolates in an Asian population, Gut; 47(1): 18-22.
In article      View Article  PubMed
 
[42]  Miehlke S, Kibler K, Kim JG, Figura N, Small SM, Graham DY et al. (1996). Allelic variation in the cagA gene of Helicobacter pylori obtained from Korea compared to the United States, American Journal of Gastroenterology, 91(7).
In article      PubMed
 
[43]  Ghotaslou R, Milani M, Akhi MT, Nahaei MR, Hasani A, Hejazi MS, Meshkini M. (2013). Diversity of Helicobacter pylori cagA and vacA genes and its relationship with clinical outcomes in Azerbaijan, Iran. Adv. Pharmaceut. Bull. 3: 57-62.
In article      PubMed  PubMed
 
[44]  Zhou J, Zhang J, Xu C and He L. (2004), cagA pylori genotype and variants in Chinese Helicobacter pylori strains and relationship to gastroduodenal diseases. Journal of Medical Microbiology, 53: 231-235.
In article      View Article  PubMed
 
[45]  Parsonnet J, Replogle M, Yang S, Hiatt R (1997). Seroprevalence of CagA-Positive Strains among Helicobacter pylori-Infected, Healthy Young Adults. Journal of Infectious Diseases, 175 (5): 1240-1242.
In article      View Article  PubMed