Skip to main content
Log in

Sequence Analysis of East Asian cagA of Helicobacter pylori Isolated from Asymptomatic Healthy Japanese and Thai Individuals

  • Published:
Current Microbiology Aims and scope Submit manuscript

Abstract

CagA, especially East Asian type, is one of the most important virulence factors of Helicobacter pylori, which is believed to contribute to the gastric cancer development. There is extreme sequence heterogeneity on 3′ region of cagA gene, demonstrated by the sequence analysis of cagA of H. pylori strains isolated from gastric disease patients. However, whether such heterogeneity of the cagA gene sequence is related to the pathogenicity of H. pylori in the gastric cancer development is not certain. Therefore, in this study, the 3′ region of cagA sequences isolated from asymptomatic healthy individuals in Japan and Thailand, which show high and low gastric cancer prevalence, respectively, were analyzed and compared with those from patients with gastric cancer. The CagA sequences analysis in 21 and 12 H. pylori DNA samples obtained from Japanese and Thai individuals, respectively, by the molecular phylogenetic method showed that the sequences were more conserved in the Thai individuals (concordance rates among Thai sequences, 93.9–100%) than in the Japanese individuals (concordance rates among Japanese sequences, 82.8–100%) as shown by unrooted neighbor-joining (N-J) consensus trees constructed with the sequence between Asn869 and Ala967 in CagA. CagA sequences in gastric cancer patients were obtained from published data; analysis of these sequences revealed that CagA sequences from almost all Thai individuals were concentrated in one branch. In contrast, CagA sequences from Japanese individuals were uniformly distributed throughout the N-J consensus tree. These results suggest that the difference in the CagA sequences between asymptomatic healthy Japanese and Thai individuals may be linked to the incidence of gastric cancer in Japan and Thailand.

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.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Anwar W, Armstrong BK, Correa P, Forman D, Gentile JM, Haswell-Elkins M, Ishii A, Kaufman DG, Kuipers EJ, Lee A, Mahmoud AAF, Mégraud F, Mott KE, Rim H-J, Shirai T, Sipponen P, Taylor MG, Thamavit W (1994) Infection with Helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum 61:177–240

    Google Scholar 

  2. Azuma T (2004) Helicobacter pylori CagA protein variation associated with gastric cancer in Asia. J Gastroenterol 39:97–103

    Article  PubMed  CAS  Google Scholar 

  3. Azuma T, Yamakawa A, Yamazaki S, Fukuta K, Ohtani M, Ito Y, Dojo M, Yamazaki Y, Kuriyama M (2002) Correlation between variation of the 3′ region of the cagA gene in Helicobacter pylori and disease outcome in Japan. J Infect Dis 186:1621–1630

    Article  PubMed  CAS  Google Scholar 

  4. Churin Y, Al-Ghoul L, Kepp O, Meyer TF, Birchmeier W, Naumann M (2003) Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response. J Cell Biol 161:249–255

    Article  PubMed  CAS  Google Scholar 

  5. Covacci A, Censini S, Bugnoli M, Petracca R, Burroni D, Macchia G, Massone A, Papini E, Xiang Z, Figura N et al (1993) Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci USA 90:5791–5795

    Article  PubMed  CAS  Google Scholar 

  6. Evans DJ Jr, Queiroz DM, Mendes EN, Evans DG (1998) Diversity in the variable region of Helicobacter pylori cagA gene involves more than simple repetition of a 102-nucleotide sequence. Biochem Biophys Res Commun 245:780–784

    Article  PubMed  CAS  Google Scholar 

  7. Fu HY, Asahi K, Hayashi Y, Eguchi H, Murata H, Tsujii M, Tsuji S, Azuma T, Kawano S (2007) East Asian-type Helicobacter pylori cytotoxin-associated gene A protein has a more significant effect on growth of rat gastric mucosal cells than the Western type. J Gastroenterol Hepatol 22:355–362

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. Higashi H, Tsutsumi R, Fujita A, Yamazaki S, Asaka M, Azuma T, Hatakeyama M (2002) Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci USA 99:14428–14433

    Article  PubMed  CAS  Google Scholar 

  10. Higashi H, Tsutsumi R, Muto S, Sugiyama T, Azuma T, Asaka M, Hatakeyama M (2002) SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science 295:683–686

    Article  PubMed  CAS  Google Scholar 

  11. Hirai I, Sasaki T, Fujimoto S, Moriyama T, Azuma T, Yamamoto Y (2009) A method for assessment of Helicobacter pylori genotype using stool specimens. FEMS Immunol Med Microbiol 56:63–66

    Article  PubMed  CAS  Google Scholar 

  12. Hirai I, Sasaki T, Kimoto A, Fujimoto S, Moriyama T, Yamamoto Y (2009) Assessment of East Asian-type cagA-positive Helicobacter pylori using stool specimens from asymptomatic healthy Japanese individuals. J Med Microbiol 58:1149–1153

    Article  PubMed  CAS  Google Scholar 

  13. Hirai I, Sasaki T, Kimoto A, Yamamoto Y, Azuma T, Mahachai V, Hansomburana P, Lertkupinit C, Luangjaru S, Noophan P, Chanatrirattanapan R, Piyanirandr V, Sappajit T, Suthivarakom K, Sangsuk L, Wangroongsarb P (2010) Infection of less virulent Helicobacter pylori strains in asymptomatic healthy individuals in Thailand as a potential contributing factor to the Asian enigma. Microbes Infect 12:227–230

    Article  PubMed  Google Scholar 

  14. Hirata Y, Yanai A, Shibata W, Mitsuno Y, Maeda S, Ogura K, Yoshida H, Kawabe T, Omata M (2004) Functional variability of cagA gene in Japanese isolates of Helicobacter pylori. Gene 343:165–172

    Article  PubMed  CAS  Google Scholar 

  15. Hoshino FB, Katayama K, Watanabe K, Takahashi S, Uchimura H, Ando T (2000) Heterogeneity found in the cagA gene of Helicobacter pylori from Japanese and non-Japanese isolates. J Gastroenterol 35:890–897

    Article  PubMed  CAS  Google Scholar 

  16. Kanada R, Uchida T, Tsukamoto Y, Nguyen LT, Hijiya N, Matsuura K, Kodama M, Okimoto T, Murakami K, Fujioka T, Yanagisawa S, Moriyama M (2008) Genotyping of the cagA gene of Helicobacter pylori on immunohistochemistry with East Asian CagA-specific antibody. Pathol Int 58:218–225

    Article  PubMed  CAS  Google Scholar 

  17. Konturek PC, Konturek SJ, Brzozowski T (2009) Helicobacter pylori infection in gastric cancerogenesis. J Physiol Pharmacol 60:3–21

    PubMed  CAS  Google Scholar 

  18. Lee IO, Kim JH, Choi YJ, Pillinger MH, Kim SY, Blaser MJ, Lee YC (2010) Helicobacter pylori CagA phosphorylation status determines the gp130-activated SHP2/ERK and JAK/STAT signal transduction pathways in gastric epithelial cells. J Biol Chem 285:16042–16050

    Article  PubMed  CAS  Google Scholar 

  19. Mimuro H, Suzuki T, Tanaka J, Asahi M, Haas R, Sasakawa C (2002) Grb2 is a key mediator of Helicobacter pylori CagA protein activities. Mol Cell 10:745–755

    Article  PubMed  CAS  Google Scholar 

  20. Miwa H, Go MF, Sato N (2002) H. pylori and gastric cancer: the Asian enigma. Am J Gastroenterol 97:1106–1112

    Article  PubMed  Google Scholar 

  21. Nagy TA, Frey MR, Yan F, Israel DA, Polk DB, Peek RM Jr (2009) Helicobacter pylori regulates cellular migration and apoptosis by activation of phosphatidylinositol 3-kinase signaling. J Infect Dis 199:641–651

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  23. Sasaki T, Hirai I, Niki M, Nakamura T, Komalamisra C, Maipanich W, Kusolsuk T, Sa-Nguankiat S, Pubampen S, Yamamoto Y (2010) High prevalence of CTX-M beta-lactamase-producing Enterobacteriaceae in stool specimens obtained from healthy individuals in Thailand. J Antimicrob Chemother 65:666–668

    Article  PubMed  CAS  Google Scholar 

  24. Singh K, Ghoshal UC (2006) Causal role of Helicobacter pylori infection in gastric cancer: an Asian enigma. World J Gastroenterol 12:1346–1351

    PubMed  Google Scholar 

  25. Sugiyama T (2004) Development of gastric cancer associated with Helicobacter pylori infection. Cancer Chemother Pharmacol 54(Suppl 1):S12–S20

    PubMed  CAS  Google Scholar 

  26. Suzuki M, Mimuro H, Suzuki T, Park M, Yamamoto T, Sasakawa C (2005) Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion. J Exp Med 202:1235–1247

    Article  PubMed  CAS  Google Scholar 

  27. Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599

    Article  PubMed  CAS  Google Scholar 

  28. Truong BX, Mai VT, Tanaka H, Ly le T, Thong TM, Hai HH, Van Long D, Furumatsu K, Yoshida M, Kutsumi H, Azuma T (2009) Diverse characteristics of the CagA gene of Helicobacter pylori strains collected from patients from southern vietnam with gastric cancer and peptic ulcer. J Clin Microbiol 47:4021–4028

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Itaru Hirai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hirai, I., Yoshinaga, A., Kimoto, A. et al. Sequence Analysis of East Asian cagA of Helicobacter pylori Isolated from Asymptomatic Healthy Japanese and Thai Individuals. Curr Microbiol 62, 855–860 (2011). https://doi.org/10.1007/s00284-010-9797-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00284-010-9797-9

Keywords

Navigation