Skip to main content

Advertisement

SpringerLink
Log in

Evaluation of Helicobacter pylori vacA Genotypes in Iranian Patients with Peptic Ulcer Disease

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Helicobacter pylori is the major cause of active chronic gastritis and peptic ulcers in humans and has been linked to gastric carcinoma and lymphoma. The vacuolating cytotoxin vacA and cag pathogenicity island (cag PAI) are two identified virulence factors that are considered to have an important role in the pathogenesis of H. pylori infection. The aim of this study is to investigate the H. pylori vacA alleles in Iranian patients with peptic ulcer disease. In order to investigate this, biopsy specimens were obtained from 84 patients with gastric ulcer, gastritis, and duodenal ulcer. DNA extraction and PCR were used to detect the presence or absence of glmM, cagA and to assess the polymorphism of vacA. Of the 77 glmM PCR-positive biopsy specimens, 55 (71%) had the vacA signal sequence genotype s1, and 22 (29%) had subtype s2. vacA mid-region analysis revealed that 31 (40%) were vacA m1 and 46 (60%) were m2. The presence of the cagA gene correlated with vacA signal sequence type s1, whereas type s2 was predominantly found in cagA-negative samples (P < 0.001). Thus, the detection of vacA and cagA, virulence markers described in several clinical outcomes may be used to help the treatment and prevention of H. pylori in Iran.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Covacci A, Telford JL, Del Giudice G, Parsonnet J, Rappuoli R. Helicobacter pylori virulence and genetic geography. Science. 1999;284:1328–1333. doi:10.1126/science.284.5418.1328.

    Article  PubMed  CAS  Google Scholar 

  2. Graham DY, Yamaoka YH. Pylori and cagA: relationships with gastric cancer, duodenal ulcer, and reflux esophagitis and its complications. Helicobacter. 1998;3:145–151. doi:10.1046/j.1523-5378.1998.08031.x.

    Article  PubMed  CAS  Google Scholar 

  3. Peek RM Jr, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer. 2002;2:28–37. doi:10.1038/nrc703.

    Article  PubMed  CAS  Google Scholar 

  4. Blaser MJ, Atherton JC. Helicobacter pylori persistence: biology and disease. J Clin Invest. 2004;113:321–333.

    PubMed  CAS  Google Scholar 

  5. Erzin Y, Koksal V, Altun S, et al. Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA, babA2 genotypes and correlation with clinical outcome in Turkish patients with dyspepsia. Helicobacter. 2006;11:574–580. doi:10.1111/j.1523-5378.2006.00461.x.

    Article  PubMed  CAS  Google Scholar 

  6. Atherton JC, Peek RM Jr, Tham KT, Cover TL, Blaser MJ. Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology. 1997;112:92–99. doi:10.1016/S0016-5085(97)70223-3.

    Article  PubMed  CAS  Google Scholar 

  7. van Doorn LJ, Figueiredo C, Sanna R, et al. Expanding allelic diversity of Helicobacter pylori vacA. J Clin Microbiol. 1998;36:2597–2603.

    PubMed  Google Scholar 

  8. Censini S, Lange C, Xiang Z, et al. cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci USA. 1996;93:14648–14653. doi:10.1073/pnas.93.25.14648.

    Article  PubMed  CAS  Google Scholar 

  9. Covacci A, Censini S, Bugnoli M, et al. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci USA. 1993;90:5791–5795. doi:10.1073/pnas.90.12.5791.

    Article  PubMed  CAS  Google Scholar 

  10. Tummuru MKR, Cover TL, Blaser MJ. Cloning and expression of a high molecular weight major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun. 1993;61:1799–1809.

    PubMed  CAS  Google Scholar 

  11. Yamaoka Y, Kodama T, Kashima K, Graham DY, Sepulveda AR. Variants of the 3′ region of the cagA gene in Helicobacter pylori isolates from patients with different H. pylori-associated diseases. J Clin Microbiol. 1998;36:2258–2263.

    PubMed  CAS  Google Scholar 

  12. Stein M, Rappuoli R, Covacci A. Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation. Proc Natl Acad Sci USA. 2000;97:1263–1268. doi:10.1073/pnas.97.3.1263.

    Article  PubMed  CAS  Google Scholar 

  13. Hatakeyama M. Helicobacter pylori CagA as a potential bacterial oncoprotein in gastric carcinogenesis. Pathol Biol (Paris). 2003;51:393–394. doi:10.1016/S0369-8114(03)00026-9.

    Google Scholar 

  14. Xiang Z, Censini S, Bayeli PF, et al. Analysis of expression of CagA and VacA virulence factors in 43 strains of Helicobacter pylori reveals that clinical isolates can be divided into two major types and that CagA is not necessary for expression of the vacuolating cytotoxin. Infect Immun. 1995;63:94–98.

    PubMed  CAS  Google Scholar 

  15. Ito Y, Azuma T, Ito S, et al. Analysis and typing of the vacA gene from cagA-positive strains of Helicobacter pylori isolated in Japan. J Clin Microbiol. 1997;35:1710–1714.

    PubMed  CAS  Google Scholar 

  16. Miehlke S, Kibler K, Kim JG, et al. Allelic variation in the cagA gene of Helicobacter pylori obtained from Korea compared to the United States. Am J Gastroenterol. 1996;91:1322–1325.

    PubMed  CAS  Google Scholar 

  17. Zhang Y, Liu H, Zhou K. Lack of correlation of vacA genotype, cagA gene of Helicobacter pylori and their expression products with various gastroduodenal diseases. Chin Med J (Engl). 2001;114:703–706.

    CAS  Google Scholar 

  18. Cover TL, Blaser MJ. Purification and characterization of the vacuolating toxin from Helicobacter pylori. J Biol Chem. 1992;267:10570–10575.

    PubMed  CAS  Google Scholar 

  19. Atherton JC, Cao P, Peek RM Jr, Tummuru MK, Blaser MJ, Cover TL. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem. 1995;270:17771–17777. doi:10.1074/jbc.270.30.17771.

    Article  PubMed  CAS  Google Scholar 

  20. Marais A, Mendz GL, Hazell SL, Megraud F. Metabolism and genetics of Helicobacter pylori: the genome era. Microbiol Mol Biol Rev. 1999;63:642–674.

    PubMed  CAS  Google Scholar 

  21. Pai R, Cover TL, Tarnawski AS. Helicobacter pylori vacuolating cytotoxin (VacA) disorganizes the cytoskeletal architecture of gastric epithelial cells. Biochem Biophys Res Commun. 1999;262:245–250. doi:10.1006/bbrc.1999.1194.

    Article  PubMed  CAS  Google Scholar 

  22. Cover TL, Krishna US, Israel DA, Peek RM Jr. Induction of gastric epithelial cell apoptosis by Helicobacter pylori vacuolating cytotoxin. Cancer Res. 2003;63:951–957.

    PubMed  CAS  Google Scholar 

  23. Papini E, Zoratti M, Cover TL. In search of the Helicobacter pylori VacA mechanism of action. Toxicon. 2001;39:1757–1767. doi:10.1016/S0041-0101(01)00162-3.

    Article  PubMed  CAS  Google Scholar 

  24. Kate V, Ananthakrishnan N, Badrinath S. Can fall in anti-H. pylori IgG titres indicate eradication? J Assoc Physicians India. 2002;50:689–691.

    PubMed  CAS  Google Scholar 

  25. Reinbach DH, Cruickshank G, McColl KE. Acute perforated duodenal ulcer is not associated with Helicobacter pylori infection. Gut. 1993;34:1344–1347. doi:10.1136/gut.34.10.1344.

    Article  PubMed  CAS  Google Scholar 

  26. van Doorn LJ. Detection of Helicobacter pylori virulence-associated genes. Expert Rev Mol Diagn. 2001;1:290–298. doi:10.1586/14737159.1.3.290.

    Article  PubMed  Google Scholar 

  27. van Doorn LJ, Figueiredo C, Sanna R, et al. Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology. 1998;115:58–66. doi:10.1016/S0016-5085(98)70365-8.

    Article  PubMed  Google Scholar 

  28. Siavoshi F, Malekzadeh R, Daneshmand M, Smoot DT, Ashktorab H. Association between Helicobacter pylori in gastric cancer, ulcers and in Iranian patients. Helicobacter. 2004;9:470. doi:10.1111/j.1083-4389.2004.00256.x.

    Article  PubMed  Google Scholar 

  29. Atherton JCH. Pylori virulence factors. Br Med Bull. 1998;54:105–120.

    PubMed  CAS  Google Scholar 

  30. Nogueira C, Figueiredo C, Carneiro F, et al. Helicobacter pylori genotypes may determine gastric histopathology. Am J Pathol. 2001;158:647–654.

    PubMed  CAS  Google Scholar 

  31. De Gusmão VR, Nogueira Mendes E, De Magalhães Queiroz DM, et al. vacA genotypes in Helicobacter pylori strains isolated from children with and without duodenal ulcer in Brazil. J Clin Microbiol. 2000;38:2853–2857.

    PubMed  Google Scholar 

  32. Papini E, Gottardi E, Satin B, et al. The vacuolar ATPase proton pump is present on intracellular vacuoles induced by Helicobacter pylori. J Med Microbiol. 1996;45:84–89.

    Article  PubMed  CAS  Google Scholar 

  33. Montecucco C, Papini E, de Bernard M, Zoratti M. Molecular and cellular activities of Helicobacter pylori pathogenic factors. FEBS Lett. 1999;452:16–21. doi:10.1016/S0014-5793(99)00652-3.

    Article  PubMed  CAS  Google Scholar 

  34. Pagliaccia C, de Bernard M, Lupetti P, et al. The m2 form of the Helicobacter pylori cytotoxin has cell type-specific vacuolating activity. Proc Natl Acad Sci USA. 1998;95:10212–10217. doi:10.1073/pnas.95.17.10212.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The author would like to thank everyone at the Molecular Genetics Laboratory, Department of Biology, University of Guilan, Iran for their help. We also thank Dr. Farhad Mashayekhi and Masoud Kazemi, Department of Biology, University of Guilan, Iran for their useful comments.

Author information

Authors and Affiliations

  1. Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran

    Zivar Salehi & Mohammad Halimi Jelodar

  2. Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Putra, Serdang, Malaysia

    Ali Saber Hossein Abadi, Patimah B. T. Ismail & Cheah Yoke Kqueen

  3. Clinical Genetics Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, University of Putra, Serdang, Malaysia

    Behnam Kamalidehghan

Authors
  1. Zivar Salehi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ali Saber Hossein Abadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patimah B. T. Ismail
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cheah Yoke Kqueen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammad Halimi Jelodar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Behnam Kamalidehghan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zivar Salehi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Salehi, Z., Abadi, A.S.H., Ismail, P.B.T. et al. Evaluation of Helicobacter pylori vacA Genotypes in Iranian Patients with Peptic Ulcer Disease. Dig Dis Sci 54, 2399–2403 (2009). https://doi.org/10.1007/s10620-008-0633-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-008-0633-z

Keywords

Search

Navigation