Skip to main content
SpringerLink
Log in

Toll-like Receptor 2 (TLR) −196 to 174del Polymorphism in Gastro-duodenal Diseases in Japanese Population

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

Abstract

Toll-like receptors (TLRs) play important roles in the signaling of many pathogen-related molecules and endogenous proteins associated with immune activation. −196 to −174del polymorphism affects the TLR2 gene and alters its promoter activity. We investigated the influence of TLR2 −196 to −174del polymorphism on the risk of gastro-duodenal diseases, on the severity of Helicobacter pylori-induced gastritis in a Japanesepopulation. The study was performed on 309 patients with abdominal discomfort and 146 healthy controls. −196 to −174del polymorphism of TLR2 was investigated by allele-specific polymerase chain reaction method in all of the subjects. Gastritis scores of antral gastric mucosa were assessed according to the updated Sydney system in H. pylori-positive subjects (n = 156). Patients with abdominal discomfort was consisted of 80 gastric ulcers (25.9%), 38 duodenal ulcers (12.3%), five gastric + duodenal ulcers (1.6%), 105 patients with gastritis (34.0%) and 81 normal healthy stomachs (26.2%). We did not find any association between TLR2 polymorphism and risk of gastric ulcer, duodenal ulcer, gastric and duodenal ulcer and gastritis compared to healthy controls. However, the TLR2−196 to −174ins allele was associated with severity of intestinal metaplasia in more than 60 years of ages (P = 0.02). The same allele also increased the risks of developing more severe gastric mucosal atrophy and intestinal metaplasia in female subjects (P < 0.05, P = 0.07 respectively). No association was observed between TLR2 polymorphism and severity of neutrophil and mononuclear cell infiltration. Our data suggest that the TLR2−196 to −174ins allele was associated with more severe intestinal metaplasia in patients older than was correlated with severity of gastric mucosal atrophy and intestinal metaplasia in female subjects.

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

Similar content being viewed by others

References

  1. NIH Consensus Conference (1994) Helicobacter pylori in peptic ulcer disease. NIH consensus development panel on Helicobacter pylori in peptic ulcer disease. JAMA 272:65–69

    Article  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  CAS  Google Scholar 

  3. Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, Sibley RK (1991) Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 325:1127–1131

    Article  PubMed  CAS  Google Scholar 

  4. Huang JQ, Sridhar S, Chen Y, Hunt RH (1998) Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology 114:1169–1179

    Article  PubMed  CAS  Google Scholar 

  5. Blaser MJ, Parsonnet J (1994) Parasitism by the “slow” bacterium Helicobacter pylori leads to altered gastric homeostasis and neoplasia. J Clin Invest 94:4–8

    Article  PubMed  CAS  Google Scholar 

  6. Meyer-ter-Vehn T, Covacci A, Kist M, Pahl HL (2000) Helicobacter pylori activates mitogen-activated protein kinase cascades and induces expression of the proto-oncogenes c-fos and c-jun. J Biol Chem 275:16064–16072

    Article  PubMed  CAS  Google Scholar 

  7. Keates S, Hitti YS, Upton M, Kelly CP (1997) Helicobacter pylori infection activates NF-kappa B in gastric epithelial cells. Gastroenterology 113:1099–1109

    Article  PubMed  CAS  Google Scholar 

  8. Maeda S, Akanuma M, Mitsuno Y, Hirata Y, Ogura K, Yoshida H, Shiratori Y, Omata M (2001) Distinct mechanism of Helicobacter pylori-mediated NF-kappa B activation between gastric cancer cells and monocytic cells. J Biol Chem 276:44856–44864

    Article  PubMed  CAS  Google Scholar 

  9. Aihara M, Tsuchimoto D, Takizawa H, Azuma A, Wakebe H, Ohmoto Y, Imagawa K, Kikuchi M, Mukaida N, Matsushima K (1997) Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45. Infect Immun 65:3218–3224

    PubMed  CAS  Google Scholar 

  10. Crowe SE, Alvarez L, Dytoc M, Hunt RH, Muller M, Sherman P, Patel J, Jin Y, Ernst PB (1995) Expression of interleukin 8 and CD54 by human gastric epithelium after Helicobacter pylori infection in vitro. Gastroenterology 108:65–74

    Article  PubMed  CAS  Google Scholar 

  11. Akira S, Takeda K, Kaisho T (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2:675–680

    Article  PubMed  CAS  Google Scholar 

  12. Underhill DM, Ozinsky A (2002) Toll-like receptors: key mediators of microbe detection. Curr Opin Immunol 14:103–110

    Article  PubMed  CAS  Google Scholar 

  13. Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1:135–45

    Article  PubMed  CAS  Google Scholar 

  14. Schnare M, Barton GM, Holt AC, Takeda K, Akira S, Medzhitov R (2001) Toll-like receptors control activation of adaptive immune responses. Nat Immunol 2:947–950

    Article  PubMed  CAS  Google Scholar 

  15. Ozinsky A, Underhill DM, Fontenot JD, Hajjar AM, Smith KD, Wilson CB, Schroeder L, Aderem A (2000) The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci USA 97:13766–13771

    Article  PubMed  CAS  Google Scholar 

  16. Ding SZ, Torok AM, Smith MF Jr, Goldberg JB (2005) Toll-like receptor 2-mediated gene expression in epithelial cells during Helicobacter pylori infection. Helicobacter 10:193–204

    Article  PubMed  CAS  Google Scholar 

  17. Smith MF Jr, Mitchell A, Li G, Ding S, Fitzmaurice AM, Ryan K, Crowe S, Goldberg JB (2003) Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B activation and chemokine expression by epithelial cells. J Biol Chem 278:32552–32560

    Article  PubMed  CAS  Google Scholar 

  18. Noguchi E, Nishimura F, Fukai H, Kim J, Ichikawa K, Shibasaki M, Arinami T (2004) An association study of asthma and total serum immunoglobin E levels for toll-like receptor polymorphisms in a Japanese population. Clin Exp Allergy 34:177–183

    Article  PubMed  CAS  Google Scholar 

  19. Dixon MF, Genta RM, Yardley JH, Correa P (1996) Classification and grading of gastritis. The updated Sydney system. International workshop on the histopathology of gastritis, Houston 1994. Am J Surg Pathol 20:1161–1181

    Article  PubMed  CAS  Google Scholar 

  20. Watabe H, Mitsushima T, Yamaji Y, Okamoto M, Wada R, Kokubo T, Doi H, Yoshida H, Kawabe T, Omata M (2005) Predicting the development of gastric cancer from combining Helicobacter pylori antibodies and serum pepsinogen status: a prospective endoscopic cohort study. Gut 54:764–768

    Article  PubMed  CAS  Google Scholar 

  21. Correa P (1995) Helicobacter pylori and gastric carcinogenesis. Am J Surg Pathol 19 (Suppl1):S37–43

    PubMed  Google Scholar 

  22. El-Omar EM, Penman ID, Ardill JE, Chittajallu RS, Howie C, McColl KE (1995) Helicobacter pylori infection and abnormalities of acid secretion in patients with duodenal ulcer disease. Gastroenterology 109:681–691

    Article  PubMed  CAS  Google Scholar 

  23. Lee S, Iida M, Yao T, Shindo S, Nose Y, Akazawa K, Okabe H, Fujishima M (1990) Risk of gastric cancer in patients with non-surgically treated peptic ulcer. Scand J Gastroenterol 25:1223–1226

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan

    Tomomitsu Tahara, Tomiyasu Arisawa, Fangyu Wang, Tomoyuki Shibata, Masakatsu Nakamura, Mikijyu Sakata, Ichiro Hirata & Hiroshi Nakano

Authors
  1. Tomomitsu Tahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tomiyasu Arisawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fangyu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tomoyuki Shibata
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masakatsu Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mikijyu Sakata
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ichiro Hirata
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hiroshi Nakano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tomomitsu Tahara.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tahara, T., Arisawa, T., Wang, F. et al. Toll-like Receptor 2 (TLR) −196 to 174del Polymorphism in Gastro-duodenal Diseases in Japanese Population. Dig Dis Sci 53, 919–924 (2008). https://doi.org/10.1007/s10620-007-9950-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-007-9950-x

Keywords

Search

Navigation