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Analysis of the 3′ Variable Region of the cagA Gene of Helicobacter pylori Isolated in Koreans

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Abstract

CagA protein of Helicobacter pylori is injected into epithelial cells, and it undergoes tyrosine phosphorylation, resulting in inducing cytoskeletal rearrangements. A few studies have suggested that the number of CagA tyrosine phosphorylation motifs (EPIYA) and subtypes of CagA were associated with gastric cancer. This study was performed to characterize the 3' variable regions of the cagA gene of H. pylori and to investigate whether or not there is any relationship between the diversities of cagA and the disease outcome in Korea. Seventy-nine patients (chronic gastritis, 15; duodenal ulcer, 27; benign gastric ulcer, 18; gastric cancer, 19) were enrolled. Biopsy specimens were taken from the antrum for H. pylori culture, and genomic DNA was extracted. PCR and DNA sequence analysis was carried out for the 3′ variable region of the cagA gene. Seventy-eight strains (98.8%) contained three EPIYA motifs and one strain (1.2%) isolated from a patient with duodenal ulcer contained four EPIYA motifs. Seventy-six strains (96.2%) were the East Asian type. In conclusion, there was no significant difference between the number of EPIYA motifs or CagA subtypes and various gastroduodenal diseases in Korea.

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References

  1. Peek RM Jr, Blaser MJ (2002) Helicobacter pylori and gastrointestinal tract adenocarcinomas. Natl Rev Cancer 2:28–37

    Google Scholar 

  2. Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ (2001) Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 345:784–789

    Article  PubMed  Google Scholar 

  3. Wong BC, Lam SK, Wong WM, Chen JS, Zheng TT, Feng RE, Lai KC, Hu WH, Yuen ST, Leung SY, Fong DY, Ho J, Ching CK (2004) Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA 291:187–194

    PubMed  Google Scholar 

  4. Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, Rappuoli R, Covacci A (1996) cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci USA 93:14648–14653

    Article  PubMed  Google Scholar 

  5. Kim JM, Kim JS, Jung HC, Song IS, Kim CY (2000) Virulence factors of Helicobacter pylori in Korean isolates do not influence proinflammatory cytokine gene expression and apoptosis in human gastric epithelial cells, nor do these factors influence the clinical outcome. J Gastroenterol 35:898–906

    Article  PubMed  Google Scholar 

  6. 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

    PubMed  Google Scholar 

  7. Figueiredo C, Van Doorn LJ, Nogueira C, Soares JM, Pinho C, Figueira P, Quint WG, Carneiro F (2001) Helicobacter pylori genotypes are associated with clinical outcome in Portuguese patients and show a high prevalence of infections with multiple strains. Scand J Gastroenterol 36:128–135

    Article  PubMed  Google Scholar 

  8. Jenks PJ, Megraud F, Labigne A (1998) Clinical outcome after infection with Helicobacter pylori does not appear to be reliably predicted by the presence of any of the genes of the cag pathogenicity island. Gut 43:752–758

    PubMed  Google Scholar 

  9. Maeda S, Ogura K, Yoshida H, Kanai F, Ikenoue T, Kato N, Shiratori Y, Omata M (1998) Major virulence factors, VacA and CagA, are commonly positive in Helicobacter pylori isolates in Japan. Gut 42:338–343

    Article  PubMed  Google Scholar 

  10. Park SM, Park J, Kim JG, Cho HD, Cho JH, Lee DH, Cha YJ (1998) Infection with Helicobacter pylori expressing the cagA gene is not associated with an increased risk of developing peptic ulcer diseases in Korean patients. Scand J Gastroenterol 33:923–927

    PubMed  Google Scholar 

  11. Asahi M, Azuma T, Ito S, Ito Y, Suto H, Nagai Y, Tsubokawa M, Tohyama Y, Maeda S, Omata M, Suzuki T, Sasakawa C (2000) Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells. J Exp Med 191:593–602

    Article  PubMed  Google Scholar 

  12. Selbach M, Moese S, Hauck CR, Meyer TF, Backert S (2002) Src is the kinase of the Helicobacter pylori CagA protein in vitro and in vivo. J Biol Chem 277:6775–6778

    Article  PubMed  CAS  Google Scholar 

  13. Backert S, Moese S, Selbach M, Brinkmann V, Meyer TF (2001) Phosphorylation of tyrosine 972 of the Helicobacter pylori CagA protein is essential for induction of a scattering phenotype in gastric epithelial cells. Mol Microbiol 42:631–644

    Article  PubMed  Google Scholar 

  14. 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  Google Scholar 

  15. Covacci A, Censini S, Bugnoli M, 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  Google Scholar 

  16. 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 

  17. Argent RH, Kidd M, Owen RJ, Thomas RJ, Limb MC, Atherton JC (2004) Determinants and consequences of different levels of CagA phosphorylation for clinical isolates of Helicobacter pylori. Gastroenterology 127:514–523

    Article  PubMed  CAS  Google Scholar 

  18. Yamaoka Y, Kodama T, Kashima K, Graham DY, Sepulveda AR (1998) Variants of the 3' region of the cagA gene in Helicobacter pylori isolates from patients with different H. pylori-associated diseases. J Clin Microbiol 36:2258–2263

    PubMed  Google Scholar 

  19. Azuma T, Yamazaki S, Yamakawa A, Ohtani M, Muramatsu A, Suto H, Ito Y, Dojo M, Yamazaki Y, Kuriyama M, Keida Y, Higashi H, Hatakeyama M (2004) Association between diversity in the Src homology 2 domain-containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer. J Infect Dis 189:820–827

    Article  PubMed  Google Scholar 

  20. Zhu YL, Zheng S, Du Q, Qian KD, Fang PC (2005) Characterization of CagA variable region of Helicobacter pylori isolates from Chinese patients. World J Gastroenterol 11:880–884

    PubMed  Google Scholar 

  21. Lai YP, Yang JC, Lin TZ, Wang JT, Lin JT (2003) CagA tyrosine phosphorylation in gastric epithelial cells caused by Helicobacter pylori in patients with gastric adenocarcinoma. Helicobacter 8:235–243

    Article  PubMed  Google Scholar 

  22. Murray MG, Thompson WF (1980) Rapid isolation of high molecular weight plant DNA. Nucleic Acids Res 8:4321–4325

    Article  PubMed  Google Scholar 

  23. 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  Google Scholar 

  24. De Souza D, Fabri LJ, Nash A, Hilton DJ, Nicola NA, Baca M: SH2 domains from suppressor of cytokine signaling-3 and protein tyrosine phosphatase SHP-2 have similar binding specificities. Biochemistry 41:9229–9236

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

    Google Scholar 

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Acknowledgments

This work was supported by Grant 02-03-001 from the SNUBH Research fund. We appreciate the skillful assistance of Mi Soon Kim.

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Authors and Affiliations

  1. Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea

    Kee Don Choi, Nayoung Kim, Dong Ho Lee, Joo Sung Kim, Hyun Chae Jung & In Sung Song

  2. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnamsi, Gyeonggi-do, Korea

    Nayoung Kim & Dong Ho Lee

  3. Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea

    Jung Mogg Kim

  4. Department of Internal Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-Gu, Sungnam-si, Kyungi-do, 463-707, Korea

    Nayoung Kim

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  1. Kee Don Choi
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  2. Nayoung Kim
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  3. Dong Ho Lee
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  4. Jung Mogg Kim
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  5. Joo Sung Kim
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Correspondence to Nayoung Kim.

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Choi, K.D., Kim, N., Lee, D.H. et al. Analysis of the 3′ Variable Region of the cagA Gene of Helicobacter pylori Isolated in Koreans. Dig Dis Sci 52, 960–966 (2007). https://doi.org/10.1007/s10620-005-9030-z

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  • DOI: https://doi.org/10.1007/s10620-005-9030-z

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