Skip to main content

Advertisement

Log in

Five-year monitoring of considerable changes in tyrosine phosphorylation motifs of the Helicobacter pylori cagA gene in Iran

  • Microbial Genetics • Original Paper
  • Published:
Journal of Applied Genetics Aims and scope Submit manuscript

Abstract

CagA is a major virulence factor of Helicobacter pylori involved in host cell modulation. The C-terminal part of CagA containing the EPIYA motifs is highly variable and is important for the biological activity of the protein. The aim of this study was consideration of the changes in cagA tyrosine phosphorylation motifs (TPMs) of H. pylori. A set of 302 H. pylori DNA samples from the Iranian population from 2006 to 2011 was selected for the proposed study. The cagA gene and its TPMs were assessed by using polymerase chain reaction (PCR) and specific primers. The prevalence of the cagA gene in our study ranged from 91.43 % to 97.06 % (with an average of 95.03 %). Out of the cagA-positive samples, the prevalence of TPMs A and B increased from 12.5 % and 23.44 % to 71.2 % and 63.63 %, respectively. Also, the prevalence of samples infected with Western and East Asian types of H. pylori ranged from 64.06 % to 5.73 % for the Western type and 17.19 % to 51.59 % for the East Asian type. Overall, our results showed a high prevalence of the cagA gene. Also, it seems that cagA TPMs of H. pylori is undergoing a change from the Western type to the East Asian type in Iran.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Acosta N, Quiroga A, Delgado P, Bravo MM, Jaramillo C (2010) Helicobacter pylori CagA protein polymorphisms and their lack of association with pathogenesis. World J Gastroenterol 16:3936–3943

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Backert S, Clyne M, Tegtmeyer N (2011) Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori. Cell Commun Signal 9:28. doi:10.1186/1478-811X-9-28

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Batista SA, Rocha GA, Rocha AMC, Saraiva IEB, Cabral MMDA, Oliveira RC, Queiroz DMM (2011) Higher number of Helicobacter pylori CagA EPIYA C phosphorylation sites increases the risk of gastric cancer, but not duodenal ulcer. BMC Microbiol 11:61

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chattopadhyay S, Patra R, Chatterjee R, De R, Alam J, Ramamurthy T, Chowdhury A, Nair GB, Berg DE, Mukhopadhyay AK (2012) Distinct repeat motifs at the C-terminal region of CagA of Helicobacter pylori strains isolated from diseased patients and asymptomatic individuals in West Bengal, India. Gut Pathog 4:4

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chomvarin C, Phusri K, Sawadpanich K, Mairiang P, Namwat W, Wongkham C, Hahnvajanawong C (2012) Prevalence of cagA EPIYA motifs in Helicobacter pylori among dyspeptic patients in Northeast Thailand. Southeast Asian J Trop Med Public Health 43:105–115

    CAS  PubMed  Google Scholar 

  • Delgado-Rosado G, Dominguez-Bello MG, Massey SE (2011) Positive selection on a bacterial oncoprotein associated with gastric cancer. Gut Pathog 3:18

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fajardo CA, Quiroga AJ, Coronado A, Labrador K, Acosta N, Delgado P, Jaramillo C, Bravo MM (2013) CagA EPIYA polymorphisms in Colombian Helicobacter pylori strains and their influence on disease-associated cellular responses. World J Gastrointest Oncol 5(3):50–59. doi:10.4251/wjgo.v5.i3.50

    Article  PubMed Central  PubMed  Google Scholar 

  • Kargar M, Souod N, Ghorbani-Dalini S, Doosti A, Rezaeian AA (2011a) Evaluation of cagA tyrosine phosphorylation DNA motifs in Helicobacter pylori isolates from gastric disorder patients in West of Iran. Sci Res Essays 6:6454–6458

    CAS  Google Scholar 

  • Kargar M, Souod N, Doosti A, Ghorbani-Dalini S (2011b) Prevalence of Helicobacter pylori vacuolating cytotoxin A gene as a predictive marker for different gastrodoudenal diseases. Iran J Clin Infect Dis 6:85–89

    CAS  Google Scholar 

  • Kargar M, Baghernejad M, Doosti A, Ghorbani-Dalini S (2011c) Clarithromycin resistance and 23S rRNA mutations in Helicobacter pylori isolates in Iran. Afr J Microbiol Res 5:853–856

    CAS  Google Scholar 

  • Kargar M, Baghernejad M, Doosti A, Ghorbani-Dalini S (2011d) Clarithromycin resistance and 23S rRNA mutations in Helicobacter pylori. In: Pascu O (ed) Gastrointestinal endoscopy. InTech, Croatia, pp 99–124

    Google Scholar 

  • Kargar M, Ghorbani-Dalini S, Doosti A, Souod N (2012a) Real-time PCR for Helicobacter pylori quantification and detection of clarithromycin resistance in gastric tissue from patients with gastrointestinal disorders. Res Microbiol 163:109–113

    Article  CAS  PubMed  Google Scholar 

  • Kargar M, Doosti A, Ghorbani-Dalini S (2012b) Detection of four clarithromycin resistance point mutations in Helicobacter pylori: comparison of real-time PCR and PCR-RFLP methods. Comp Clin Pathol 22:1007–1013. doi:10.1007/s00580-012-1519-1

    Article  Google Scholar 

  • Kawai M, Furuta Y, Yahara K, Tsuru T, Oshima K, Handa N, Takahashi N, Yoshida M, Azuma T, Hattori M, Uchiyama I, Kobayashi I (2011) Evolution in an oncogenic bacterial species with extreme genome plasticity: Helicobacter pylori East Asian genomes. BMC Microbiol 11:104

    Article  CAS  PubMed Central  PubMed  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  PubMed Central  PubMed  Google Scholar 

  • Mohamed R, Hanafiah A, Rose IM, Manaf MR, Abdullah SA, Sagap I, van Belkum A, Yaacob JA (2009) Helicobacter pylori cagA gene variants in Malaysians of different ethnicity. Eur J Clin Microbiol Infect Dis 28:865–869

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Monstein HJ, Karlsson A, Ryberg A, Borch K (2010) Application of PCR amplicon sequencing using a single primer pair in PCR amplification to assess variations in Helicobacter pylori CagA EPIYA tyrosine phosphorylation motifs. BMC Res Notes 3:35

    Article  PubMed Central  PubMed  Google Scholar 

  • Owen RJ, Sharp SI, Chisholm SA, Rijpkema S (2003) Identification of cagA tyrosine phosphorylation DNA motifs in Helicobacter pylori isolates from peptic ulcer patients by novel PCR-restriction fragment length polymorphism and real-time fluorescence PCR assays. J Clin Microbiol 41:3112–3118

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Schmidt HM, Goh KL, Fock KM, Hilmi I, Dhamodaran S, Forman D, Mitchell H (2009) Distinct cagA EPIYA motifs are associated with ethnic diversity in Malaysia and Singapore. Helicobacter 14:256–263

    Article  CAS  PubMed  Google Scholar 

  • Shokrzadeh L, Baghaei K, Yamaoka Y, Dabiri H, Jafari F, Sahebekhtiari N, Tahami A, Sugimoto M, Zojaji H, Zali MR (2010) Analysis of 3′-end variable region of the cagA gene in Helicobacter pylori isolated from Iranian population. J Gastroenterol Hepatol 25:172–177

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sicinschi LA, Correa P, Peek RM, Camargo MC, Piazuelo MB, Romero-Gallo J, Hobbs SS, Krishna U, Delgado A, Mera R, Bravo LE, Schneider BG (2010) CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions. Clin Microbiol Infect 16:369–378

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Snider JL, Allison C, Bellaire BH, Ferrero RL, Cardelli JA (2008) The β1 integrin activates JNK independent of CagA, and JNK activation is required for Helicobacter pylori CagA+-induced motility of gastric cancer cells. J Biol Chem 283:13952–13963

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tanuma M, Rimbara E, Noguchi N, Boonyaritichaikij S, Kuwabara K, Fukunaga Y, Sasatsu M (2009) Analysis of clarithromycin resistance and CagA status in Helicobacter pylori by use of feces from children in Thailand. J Clin Microbiol 47:4144–4145

    Article  PubMed Central  PubMed  Google Scholar 

  • Tiwari SK, Sharma V, Sharma VK, Gopi M, Saikant R, Nandan A, Bardia A, Gunisetty S, Katikala P, Habeeb MA, Khan AA, Habibullah CM (2011) Phylogenetic analysis, based on EPIYA repeats in the cagA gene of Indian Helicobacter pylori, and the implications of sequence variation in tyrosine phosphorylation motifs on determining the clinical outcome. Genet Mol Biol 34:280–285

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Uchida T, Nguyen LT, Takayama A, Okimoto T, Kodama M, Murakami K, Matsuhisa T, Trinh TD, Ta L, Ho DQ, Hoang HH, Kishida T, Fujioka T, Moriyama M, Yamaoka Y (2009) Analysis of virulence factors of Helicobacter pylori isolated from a Vietnamese population. BMC Microbiol 9:175

    Article  PubMed Central  PubMed  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(34):5685–5692. doi:10.3748/wjg.v19.i34.5685

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang F, Sun GP, Zou YF, Zhong F, Ma T, Li XQ, Wu D (2013) Helicobacter pylori infection predicts favorable outcome in patients with gastric cancer. Curr Oncol 20(5):e388–e395. doi:10.3747/co.20.1417

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yamaoka Y (2010) Mechanisms of disease: Helicobacter pylori virulence factors. Nat Rev Gastroenterol Hepatol 7:629–641

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

All the authors are grateful to the Jahrom and Shahrekord Branches of the Islamic Azad University, and the staff of the Biotechnology Research Center, for their executive support of this project.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mohammad Kargar.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kargar, M., Ghorbani-Dalini, S., Doosti, A. et al. Five-year monitoring of considerable changes in tyrosine phosphorylation motifs of the Helicobacter pylori cagA gene in Iran. J Appl Genetics 55, 417–422 (2014). https://doi.org/10.1007/s13353-014-0209-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13353-014-0209-x

Keywords

Navigation