Skip to main content
SpringerLink
Log in

Clinical relevance of cagL gene and virulence genotypes with disease outcomes in a Helicobacter pylori infected population from Iran

  • Original Paper
  • Published:
World Journal of Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Helicobacter pylori infection is common in Iran as in other developing countries. Certain genotypes of H. pylori have been associated with increased occurrence of chronic gastritis, peptic ulcers, and gastric adenocarcinoma. The aim of this study was to investigate the clinical relevance of cagL gene and other virulence genotypes of H. pylori isolates with clinical outcomes in Iranian patients. Totally, 126 symptomatic patients who underwent gastroduodenal endoscopy were enrolled in the study. Sixty-one H. pylori strains were isolated from the patients studied. The presence of the cagL, cagA, vacA, iceA, babA2 and sabA genes in the corresponding H. pylori isolates were determined by polymerase chain reaction and the results were compared with clinical outcomes and histopathology. The cagL, cagA, vacA s1, vacA s2, vacA m1, vacA m2, iceA1, iceA2, babA 2 , and sabA genotypes were detected in 96.7, 85.2, 75.4, 24.6, 29.5, 70.5, 42.6, 23, 96.7, and 83.6 % of the isolates, respectively. The three genotypic combinations, cagL/cagA/vacAs1m1/iceA1/babA2/sabA, cagL/cagA/vacAs1m2/iceA1/babA2/sabA, and cagL/cagA/vacAs1m2/iceA2/babA2/sabA were determined as the most prevalent combined genotypes. There was a significant correlation between the presence of cagL gene and cagA positivity (P = 0.02). No significant correlation was found between the various genotypes and clinical outcomes (P > 0.05). The present study showed a very high prevalence of cagL genotype among the H. pylori isolates from Iranian patients. Our results demonstrated that neither single genotype nor combination genotypes of virulence-associated genes was significantly helpful markers for predicting the severity of gastroduodenal disease associated with H. pylori infection in Iranian patients.

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

Similar content being viewed by others

References

  • Amieva MR, El-Omar EM (2008) Host-bacterial interactions in Helicobacter pylori infection. Gastroenterology 134:306–323

    Article  CAS  Google Scholar 

  • Arents NL, van-Zwet AA, Thijs JC, Kooistra-Smid AM, Van Slochteren KR, Degener JE, Kleibeuker JH, Van Doorn LJ (2001) The importance of vacA, cagA, and iceA genotypes of Helicobacter pylori infection in peptic ulcer disease and gastroesophageal reflux disease. Am J Gastroenterol 96:2603–2608

    Article  CAS  Google Scholar 

  • Ashour AA, Collares GB, Mendes EN, de Gusmão VR, Queiroz DM, Magalhães PP, de Carvalho AS, de Oliveira CA, Nogueira AM, Rocha GA, Rocha AM (2001) IceA genotypes of Helicobacter pylori strains isolated from Brazilian children and adults. J Clin Microbiol 39:1746–1750

    Article  CAS  Google Scholar 

  • Asrat D, Nilsson I, Mengistu Y, Kassa E, Ashenafi S, Ayenew K, Wadström T, Abu-Al-Soud W (2004) Prevalence of Helicobacter pylori vacA and cagA genotypes in Ethiopian dyspeptic patients. J Clin Microbiol 42:2682–2684

    Article  CAS  Google Scholar 

  • Atherton JC, Blaser MJ (2009) Coadaptation of Helicobacter pylori and humans: ancient history, modern implications. J Clin Investig 119:2475–2487

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Azevedo NF, Huntington J, Goodman KJ (2009) The epidemiology of Helicobacter pylori and public health implications. Helicobacter 14(Suppl. 1):1–7

    Article  Google Scholar 

  • Backert S, Naumann M (2010) What a disorder: proinflammatory signaling pathways induced by Helicobacter pylori. Trends Microbiol 18:479–486

    Article  CAS  Google Scholar 

  • Backert S, Tegtmeyer N (2010) The versatility of the Helicobacter pylori vacuolating cytotoxin VacA in signal transduction and molecular crosstalk. Toxins 2:69–92

    Article  CAS  Google Scholar 

  • Backert S, Tegtmeyer N, Selbach M (2010) The versatility of Helicobacter pylori CagA effector protein functions: the master key hypothesis. Helicobacter 15:163–176

    Article  CAS  Google Scholar 

  • Baghaei K, Shokrzadeh L, Jafari F, Dabiri H, Yamaoka Y, Bolfion M, Zojaji H, Aslani MM, Zali MR (2009) Determination of Helicobacter pylori virulence by analysis of the cag pathogenicity island isolated from Iranian patients. Dig Liver Dis 41:634–638

    Article  CAS  Google Scholar 

  • Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH, Stemmermann GN, Nomura A (1995) Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res 55:2111–2115

    CAS  Google Scholar 

  • Bohr UR, Primus A, Zagoura A, Glasbrenner B, Wex T, Malfertheiner P (2002) A group-specific PCR assay for the detection of Helicobacteriaceae in human gut. Helicobacter 7:378–383

    Article  CAS  Google Scholar 

  • Chiurillo MA, Moran Y, Cañas M, Valderrama E, Granda N, Sayegh M, Ramírez JL (2013) Genotyping of Helicobacter pylori virulence-associated genes shows high diversity of strains infecting patients in western Venezuela. Int J Infect Dis 17:e750–e756

    Article  CAS  Google Scholar 

  • Dabiri H, Maleknejad P, Yamaoka Y, Feizabadi MM, Jafari F, Rezadehbashi M, Nakhjavani FA, Mirsalehian A, Zali MR (2009) Distribution of Helicobacter pylori cagA, cagE, oipA and vacA in different major ethnic groups in Tehran, Iran. J Gastroenterol Hepatol 24:1380–1386

    Article  Google Scholar 

  • Erzin Y, Koksal V, Altun S, Dobrucali A, Aslan M, Erdamar S, Dirican A, Kocazeybek B (2006) Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA, babA2 genotypes and correlation with clinical outcome in Turkish patients with dyspepsia. Helicobacter 11:574–580

    Article  CAS  Google Scholar 

  • Figueiredo C, Machado JC, Pharoah P, Seruca R, Sousa S, Carvalho R, Capelinha AF, Quint W, Caldas C, van Doorn LJ, Carneiro F, Sobrinho-Simões M (2002) Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst 94:1680–1687

    Article  CAS  Google Scholar 

  • Gerhard M, Lehn N, Neumayer N, Borén T, Rad R, Schepp W, Miehlke S, Classen M, Prinz C (1999) Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin. Proc Natl Acad Sci 96:12778–12783

    Article  CAS  Google Scholar 

  • Gorrell RJ, Guan J, Xin Y, Tafreshi MA, Hutton ML, McGuckin MA, Ferrero RL, Kwok T (2013) A novel NOD1- and CagA-independent pathway of interleukin-8 induction mediated by the Helicobacter pylori type IV secretion system. Cell Microbiol 15:554–570

    Article  CAS  Google Scholar 

  • Hatakeyama M (2009) Helicobacter pylori and gastric carcinogenesis. J Gastroenterol 44:239–248

    Article  CAS  Google Scholar 

  • Hosseini E, Poursina F, de Wiele TV, Safaei HG, Adibi P (2012) Helicobacter pylori in Iran: a systematic review on the association of genotypes and gastroduodenal diseases. J Res Med Sci 17:280–292

    CAS  Google Scholar 

  • Hussein NR, Mohammadi M, Talebkhan Y, Doraghi M, Letley DP, Muhammad MK, Argent RH, Atherton JC (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. J Clin Microbiol 46:1774–1779

    Article  CAS  Google Scholar 

  • Ilver D, Arnqvist A, Ogren J, Frick IM, Kersulyte D, Incecik ET, Berg DE, Covacci A, Engstrand L, Borén T (1998) Helicobacter pylori adhesion-binding fucosylated histo-blood group antigens revealed by retagging. Science 279:373–377

    Article  CAS  Google Scholar 

  • Kauser F, Hussain MA, Ahmed I, Ahmad N, Habeeb A, Khan AA, Ahmed N (2005) Comparing genomes of Helicobacter pylori strains from the high-altitude desert of Ladakh, India. J Clin Microbiol 43:1538–1545

    Article  CAS  Google Scholar 

  • Kraft C, Suerbaum S (2005) Mutation and recombination in Helicobacter pylori: mechanisms and role in generating strain diversity. Int J Med Microbiol 295:299–305

    Article  CAS  Google Scholar 

  • Kusters JG, van Vliet AH, Kuipers EJ (2006) Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev 19:449–490

    Article  CAS  Google Scholar 

  • Kwok T, Zabler D, Urman S, Rohde M, Hartig R, Wessler S, Misselwitz R, Berger J, Sewald N, König W, Backert S (2007) Helicobacter exploits integrin for type IV secretion and kinase activation. Nature 449:862–867

    Article  CAS  Google Scholar 

  • Lage AP, Godfroid E, Fauconnier A, Burette A, Butzler JP, Bollen A, Glupczynski Y (1995) Diagnosis of Helicobacter pylori infection by PCR: comparison with other invasive techniques and detection of cagA gene in gastric biopsy specimens. J Clin Microbiol 33:2752–2756

    CAS  Google Scholar 

  • Lehours P, Ménard A, Dupouy S, Bergey B, Richy F, Zerbib F, Ruskoné-Fourmestraux A, Delchier JC, Mégraud F (2004) Evaluation of the association of nine Helicobacter pylori virulence factors with strains involved in low-grade gastric mucosa-associated lymphoid tissue lymphoma. Infect Immun 72:880–888

    Article  CAS  Google Scholar 

  • Mahdavi J, Sondén B, Hurtig M, Olfat FO, Forsberg L, Roche N, Angstrom J, Larsson T, Teneberg S, Karlsson KA, Altraja S, Wadström T, Kersulyte D, Berg DE, Dubois A, Petersson C, Magnusson KE, Norberg T, Lindh F, Lundskog BB, Arnqvist A, Hammarström L, Borén T (2002) Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science 297:573–578

    Article  CAS  Google Scholar 

  • Miernyk K, Morris J, Bruden D, McMahon B, Hurlburt D, Sacco F, Parkinson A, Hennessy T, Bruce M (2011) Characterization of Helicobacter pylori cagA and vacA genotypes among Alaskans and their correlation with clinical disease. J Clin Microbiol 49:3114–3121

    Article  CAS  Google Scholar 

  • Mukhopadhyay AK, Kersulyte D, Jeong JY, Datta S, Ito Y, Chowdhury A, Chowdhury S, Santra A, Bhattacharya SK, Azuma T, Nair GB, Berg DE (2000) Distinctiveness of genotypes of Helicobacter pylori in Calcutta, India. J Bacteriol 182:2327–3219

    Google Scholar 

  • Nouraie M, Latifi-Navid S, Rezvan H, Radmard AR, Maghsudlu M, Zaer-Rezaii H, Amini S, Siavoshi F, Malekzadeh R (2009) Childhood hygienic practice and family education status determine the prevalence of Helicobacter pylori infection in Iran. Helicobacter 14:40–46

    Article  Google Scholar 

  • Polk DB, Peek RM Jr (2010) Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer 10:403–414

    Article  CAS  Google Scholar 

  • Rhead JL, Letley DP, Mohhammadi M, Hussein N, Mohagheghi MA, Eshagh Hosseini M, Atherton JC (2007) A New Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer. Gastroenterology 133:926–936

    Article  CAS  Google Scholar 

  • Schuelein R, Everingham P, Kwok T (2011) Integrin-mediated type IV secretion by Helicobacter: what makes it tick? Trends Microbiol 19:211–216

    Article  CAS  Google Scholar 

  • Sheu BS, Sheu SM, Yang HB, Wu JJ (2003) Host gastric Lewis expression determines the bacterial density of Helicobacter pylori in babA2 genopositive infection. Gut 52:927–932

    Article  CAS  Google Scholar 

  • Sheu BS, Odenbreit S, Hung KH, Liu CP, Sheu SM, Yang HB, Wu JJ (2006) Interaction between host gastric Sialyl-Lewis X and H. pylori SabA enhances H. pylori density in patients lacking gastric Lewis B antigen. Am J Gastroenterol 101:36–44

    Article  CAS  Google Scholar 

  • Shiota S, Watada M, Matsunari O, Iwatani S, Suzuki R, Yamaoka Y (2012) Helicobacter pylori iceA, clinical outcomes, and correlation with cagA: a meta-analysis. PLoS One 7:e30354

    Article  CAS  Google Scholar 

  • Siavoshi F, Asgharzadeh A, Ghadiri H, Massarrat S, Latifi-Navid S, Zamani M (2011) Helicobacter pylori genotypes and types of gastritis in first-degree relatives of gastric cancer patients. Int J Med Microbiol 301:506–512

    Article  CAS  Google Scholar 

  • Stolte M, Meining A (2001) The updated Sydney system: classification and grading of gastritis as the basis of diagnosis and treatment. Can J Gastroenterol 15:591–598

    CAS  Google Scholar 

  • Suerbaum S, Michetti P (2002) Helicobacter pylori infection. N Engl J Med 347:175–186

    Article  Google Scholar 

  • Talebi Bezmin Abadi A, Rafiei A, Ajami A, Hosseini V, Taghvaei T, Jones KR, Merrell DS (2011) Helicobacter pylori homB, but not cagA, is associated with gastric cancer in Iran. J Clin Microbiol 49:3191–3197

    Article  Google Scholar 

  • Talebkhan Y, Mohammadi M, Mohagheghi MA, Vaziri HR, Eshagh Hosseini M, Mohajerani N, Oghalaei A, Esmaeili M, Zamaninia L (2008) CagA gene and protein status among Iranian Helicobacter pylori strains. Dig Dis Sci 53:925–932

    Article  CAS  Google Scholar 

  • Tanih NF, McMillan M, Naidoo N, Ndip LM, Weaver LT, Ndip RN (2010) Prevalence of Helicobacter pylori vacA, cagA and iceA genotypes in South African patients with upper gastrointestinal diseases. Acta Trop 116:68–73

    Article  CAS  Google Scholar 

  • Tegtmeyer N, Wessler S, Backert S (2011) Role of the cag-pathogenicity island encoded type IV secretion system in Helicobacter pylori pathogenesis. FEBS J 278:1190–1202

    Article  CAS  Google Scholar 

  • van Doorn LJ, Figueiredo C, Sanna R, Plaisier A, Schneeberger P, de Boer W, Quint W (1998) Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology 115:58–66

    Article  Google Scholar 

  • Vaziri F, Najar Peerayeh S, Alebouyeh M, Mirzaei T, Yamaoka Y, Molaei M, Maghsoudi N, Zali MR (2013) Diversity of Helicobacter pylori genotypes in Iranian patients with different gastroduodenal disorders. World J Gastroenterol 19:5685–5692

    CAS  Google Scholar 

  • Wang H, Huang S, Zhao J, Han J, Guan X, Shao S (2013) Expression of CagL from Helicobacter pylori and preliminary study of its biological function. Indian J Microbiol 53:36–40

    Article  CAS  Google Scholar 

  • Wong BC, Yin Y, Berg DE, Xia HH, Zhang JZ, Wang WH, Wong WM, Huang XR, Tang VS, Lam SK (2001) Distribution of distinct vacA, cagA and iceA alleles in Helicobacter pylori in Hong Kong. Helicobacter 6:317–324

    Article  CAS  Google Scholar 

  • Yamaoka Y, Kodama T, Kita M, Imanishi J, Kashima K, Graham DY (1998) Relationship of vacA genotypes of Helicobacter pylori to cagA status, cytotoxin production, and clinical outcome. Helicobacter 4:241–253

    Article  Google Scholar 

  • Yamaoka Y, Kodama T, Gutierrez O, Kim JG, Kashima K, Graham DY (1999) Relationship between Helicobacter pylori iceA, cagA, and vacA status and clinical outcome: studies in four different countries. J Clin Microbiol 37:2274–2279

    CAS  Google Scholar 

  • Yamaoka Y, Ojo O, Fujimoto S, Odenbreit S, Haas R, Gutierrez O, El-Zimaity HM, Reddy R, Arnqvist A, Graham DY (2006) Helicobacter pylori outer membrane proteins and gastroduodenal disease. Gut 55:775–781

    Article  CAS  Google Scholar 

  • Yanai A, Maeda S, Hikiba Y, Shibata W, Ohmae T, Hirata Y, Ogura K, Yoshida H, Omata M (2007) Clinical relevance of Helicobacter pylori sabA genotype in Japanese clinical isolates. J Gastroenterol Hepatol 22:2228–2232

    Article  CAS  Google Scholar 

  • Yeh YC, Chang WL, Yang HB, Cheng HC, Wu JJ, Sheu BS (2011) H. pylori cagL amino acid sequence polymorphism Y58E59 induces a corpus shift of gastric integrin α5β1 related with gastric carcinogenesis. Mol Carcinog 50:751–759

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors are thankful to Dr. Mahsa Molaei from the Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences. This study was funded by a research grant from the Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The project was also partially supported by a PhD grant from the Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Conflict of interest

The authors have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Abbas Yadegar & Ashraf Mohabati Mobarez

  2. Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Masoud Alebouyeh, Tabassom Mirzaei & Mohammad Reza Zali

  3. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Masoud Alebouyeh, Tabassom Mirzaei & Mohammad Reza Zali

  4. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia

    Terry Kwok

  5. Department of Microbiology, Monash University, Clayton, VIC, 3800, Australia

    Terry Kwok

Authors
  1. Abbas Yadegar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ashraf Mohabati Mobarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masoud Alebouyeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tabassom Mirzaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Terry Kwok
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mohammad Reza Zali
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ashraf Mohabati Mobarez or Masoud Alebouyeh.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yadegar, A., Mobarez, A.M., Alebouyeh, M. et al. Clinical relevance of cagL gene and virulence genotypes with disease outcomes in a Helicobacter pylori infected population from Iran. World J Microbiol Biotechnol 30, 2481–2490 (2014). https://doi.org/10.1007/s11274-014-1673-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11274-014-1673-5

Keywords

Search

Navigation