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

Ritu Saha^1, , Sharmeen Ahmed², Humayun Sattar², Maksuma Begum³, Bhuiyan Mohammad Mahtab Uddin⁴, Ahmed Abu Saleh² and Ruhul Amin Miah²

¹Department of Microbiology, Bashundhara Ad-din Medical College & Hospital, Dhaka, Bangladesh

²Department of Microbiology and Immunology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

³Department of Microbiology, Shahid Monsur Ali Medical College, Dhaka, Bangladesh

⁴Enam Medical College, Dhaka, Bangladesh

Cite this paper:
Ritu Saha, 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. 2018; 6(2):57-62. doi: 10.12691/ajmr-6-2-4

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.

Keywords:
H. pylori infection cagA gene duodenal ulcer gastric carcinoma

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References:

[1]	Atherton J. (2006). The pathogenesis of H pylori-induced gastro-duodenal diseases. Annu. Rev. Pathol;1: 63-96.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[30]	Perez‐Perez GI, Rothenbacher D, Brenner H (2004). Epidemiology of Helicobacter pylori infection. Helicobacter; 9(s1): 1-6
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[39]	Hatakeyama M & Higashi H (2005). Helicobacter pylori CagA: a new paradigm for bacterial carcinogenesis, Cancer science; 96 (12): 835-843.
[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.
[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.
[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).
[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.
[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.
[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.