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Interleukin-10 (−819 C/T) and Tumor Necrosis Factor-α (−308 G/A) Gene Variants Influence Gastritis and Lymphoid Follicle Development

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Abstract

Helicobacter pylori (H. pylori) causes gastritis, development of lymphoid follicles and later monoclonal mucosa-associated lymphoid tissue (MALT) lymphoma. We evaluated the association of tumor necrosis factor (TNF)-α (−308 G/A) and IL-10 (−819 C/T) gene polymorphisms with gastritis and lymphoid follicle formation. H. pylori infection was detected using modified Giemsa staining and IgG anti-CagA enzyme-linked immunosorbent assay (ELISA). One hundred and thirty patients with non-ulcer dyspepsia (NUD) and 200 healthy age-matched controls were genotyped for TNF-α and IL-10 polymorphisms using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). Subjects with IL-10 −819 T allele [patients (46.5%) versus controls (35.7%), p = 0.006, OR = 1.56, 95% CI = 1.14–2.15] were at risk of gastritis. Infection with H. pylori was more often associated with lymphoid follicles formation than its absence (46% versus 22%, p = 0.009). TNF-α polymorphism did not influence gastritis but patients with TNF-α −308 A allele carriers showed >2 fold risk of lymphoid follicle formation [presence (26%) versus absence (11.25%), p = 0.029, OR = 2.8; 95% CI = 1.09–7.08]. There was a trend towards association of lymphoid follicles and TNF-α −308 A allele carriers with H. pylori infection than without (58.5% versus 22.2%; p = 0.064). IL-10 −819 T and TNF-α −308 A alleles may increase risk of gastritis and lymphoid follicle formation.

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References

  1. Wotherspoon AC, Ortiz-Hidalgo C, Falzon MF et al (1991) Helicobacter pylori associated gastritis and primary B cell gastric lymphoma. Lancet 338:1175–1176

    Article  PubMed  CAS  Google Scholar 

  2. 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 

  3. Mulari A, Santi R, Palaniswamy KR et al (1994) Helicobacter pylori status in duodenal ulcer and gastric carcinoma (Abstract). Ind J Gastroenterol 13:A31

    Google Scholar 

  4. Gill HH, Desai HG, Majumdar P et al (1993) Epidemiology of H. pylori: the Indian scenario. Ind J Gastroenterol 12:9–11

    CAS  Google Scholar 

  5. Graham DY, Chakarborty K, Konar A et al (1993) H. pylori in non-ulcer dyspepsia (Abstract). Ind J Gastroenterol 12(Suppl 2):L8

    Google Scholar 

  6. Kartar S, Uday CG (2006) Causal role of Helicobacter pylori infection in gastric cancer: an Asian enigma. World J Gastroenterol 12(9):1346–1351

    Google Scholar 

  7. Wyatt JI, Rathbone BJ (1988) Immune response of the gastric mucosa to Compylobacter pylori. Scand J Gastroenterol 142(suppl):44–49

    Article  CAS  Google Scholar 

  8. Eidt S, Stolte M (1993) Prevalence of lymphoid follicles and aggregates in H. pylori gastritis in antral and body mucosa. J Clin Pathol 46:832–835

    Article  PubMed  CAS  Google Scholar 

  9. Genta RM, Hamner HW (1994) The significance of lymphoid follicles in the interpretation of gastric biopsy specimens. Arch Pathol Lab Med 118:740–743

    PubMed  CAS  Google Scholar 

  10. Chen XY, Liu WZ, Shi Y et al (2002) Helicobacter pylori associated gastric diseases and lymphoid tissue hyperplasia in gastric antral mucosa. J Clin Pathol 55:133–137

    PubMed  CAS  Google Scholar 

  11. Ghoshal UC, Tiwari S, Pandey R et al (2005) Frequency of Helicobacter pylori and CagA antibody in patients with gastric neoplasms and controls: the Indian enigma. Am J Gastroenterol 100:S64

    Article  CAS  Google Scholar 

  12. Bani-Hani KE, Yaghan RJ, Matalka II (2005) Primary gastric lymphoma in Jordan with special emphasis on descriptive epidemiology. Leukemia Lymphoma 46(9):1337–1343

    Article  PubMed  CAS  Google Scholar 

  13. Genta RM, Hamner HW, Graham DY (1993) Gastric lymphoid follicles in Helicobacter pylori infection—Frequency, distribution and response to triple therapy. Hum Pathol 24:577–583

    Article  PubMed  CAS  Google Scholar 

  14. Morse HR, Olomolaiye OO, Wood NA et al (1999) Induced heteroduplex genotyping of TNF-alpha, IL-1beta, IL-6 and IL-10 polymorphisms associated with transcriptional regulation. Cytokine 11:789–795

    Article  PubMed  CAS  Google Scholar 

  15. Santilla S, Savinainen K, Hurme M (1998) Presence of IL 1 RN allele 2 (IL1RN *2) is associated with enhanced IL1β production in vitro. Scand J Immunol 47:195–198

    Article  Google Scholar 

  16. Rad R, Prinz C, Neu B et al (2003) Synergistic effect of Helicobacter pylori virulence factors and interleukin 1 polymorphisms for the development of severe histological changes in the gastric mucosa. J Infect Dis 188:272–281

    Article  PubMed  CAS  Google Scholar 

  17. Rad R, Dossumbekova A, Neu B et al (2004) Cytokine gene polymorphism influence mucosal cytokine expression, gastric inflammation and host specific colonization during Helicobacter pylori infection. Gut 53:1082–1089

    Article  PubMed  CAS  Google Scholar 

  18. Machado JC, Figueiredo C, Canedo P et al (2003) A proinflammatory genetic profile increases the risk of chronic atrophis gastritis and gastric carcinoma. Gastroenterology 125:364–371

    Article  PubMed  CAS  Google Scholar 

  19. Bidwell J, Keen L, Gallagher G et al (1999) Cytokine gene polymorphism in human disease: on-line databases. Genes Immun 1:3–19

    Article  PubMed  CAS  Google Scholar 

  20. Furuta T, El-Omar EM, Xiao F et al (2002) Interleukin 1beta polymorphisms increase risk of hypochlorhydria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan. Gastroenterology 123(1):92–105

    Article  PubMed  CAS  Google Scholar 

  21. Perrey C, Pravica V, Sinnott PJ et al (1998) Genotyping for polymorphisms in interferon-gamma, interleukin-10, transforming growth factor-beta 1 and tumour necrosis factor-alpha genes: a technical report. Transpl Immunol 6:193–197

    Article  PubMed  CAS  Google Scholar 

  22. Kube D, Rieth H., Eskdale J et al (2001) Structural characterisation of the distal 5′ flanking region of the human interleukin-10 gene. Genes Immun 2:181–190

    Article  PubMed  CAS  Google Scholar 

  23. Dixon MF, Genta RM, Yardley JH et al (1996) Classification and grading of gastritis. The Updated Sydney System. Am J Surg Pathol 20(10):1161–1181

    Article  PubMed  CAS  Google Scholar 

  24. Wotherspoon AC, Doglioni C, Diss TC et al (1993) Regression of primary low grade gastric lymphoma of mucosal associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 342:575–577

    Article  PubMed  CAS  Google Scholar 

  25. Miller S, Dykes D et al (1998) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    Article  Google Scholar 

  26. Walston J, Sceibert M, Yen CJ et al (1999) Tumor necrosis factor α -238 and -308 polymorphisms do not associate with traits related to obesity and insulin resistance. Diabetes 48:2096–2098

    Article  PubMed  CAS  Google Scholar 

  27. Wu MS, Wu CY, Chen CJ et al (2003) Interleukin-10 genotypes associate with the risk of gastric carcinoma in Taiwanese Chinese. Int J Cancer 104:617–623

    Article  PubMed  CAS  Google Scholar 

  28. El Omar EM, Rabkin CS, Gammon MD et al (2003) Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology 124:1193–1201

    Article  PubMed  CAS  Google Scholar 

  29. Eaton KA, Mefford M, Thevenot T (2001) The role of T cell subsets and cytokines in the pathogenesis of Helicobacter pylori gastritis in mice. J Immunol 166:7456–7461

    PubMed  CAS  Google Scholar 

  30. Sutton P, Kolesnikow T, Danon S et al (2000) Dominant nonresponsiveness to Helicobacter pylori infection is associated with production of interleukin 10 but not gamma interferon. Infect Immun 68:4802–4804

    Article  PubMed  CAS  Google Scholar 

  31. Allen RD (1999) Polymorphism of the human TNF-alpha promoter—random variation or functional diversity? Mol Immunol 36:1017–1027

    Article  PubMed  CAS  Google Scholar 

  32. Messer G, Spengler U, M.C. Jung et al (1991) Polymorphic structure of the tumor necrosis factor locus: an NcoI polymorphism in the first intron of the human TNF-beta gene correlates with a variant amino acid in position 26 and a reduced level of TNF-beta production. J Exp Med 173:209–219

    Article  PubMed  CAS  Google Scholar 

  33. Ja Young L, Hak YK, Kyung HK et al (2005) Association of polymorphism of IL-10 and TNF-A genes with gastric cancer in Korea. Cancer Lett 225:207–214

    Article  CAS  Google Scholar 

  34. Abbas A.K, Murphy K.M, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383:787–793

    Article  PubMed  CAS  Google Scholar 

  35. Clerici M, Shearer G.M, Clerici E (1998) Cytokine Dysregulation in invasive cervical carcinoma and other human neoplasias: time to consider the TH1/TH2 paradigm. J Natl Cancer Inst 90:261–263

    Article  PubMed  CAS  Google Scholar 

  36. Chun L, Bing X, Yi Y et al (2005) TNF gene polymorphisms and Helicobacter pylori infection in gastric carcinogenesis in Chinese population. Am J Gastroenterol 100:290–295

    Article  CAS  Google Scholar 

  37. Perri F., Piepoli A., Bonvicini C et al (2005) Cytokine gene polymorphisms in gastric cancer patients from two Italian areas at high and low cancer prevalence. Cytokine 30:293–302

    Article  PubMed  CAS  Google Scholar 

  38. Hanninen K, Katila H, Rontu R et al (2005) Tumor necrosis factor-alpha -G308A polymorphism in schizophrenia in a Finnish population. Neurosci Lett 385:76–81

    Article  PubMed  CAS  Google Scholar 

  39. Van Doorn LJ, Figueiredo C, Sanna R et al (1999) Distinct variants of Helicobacter CagA are associated with VacA subtypes. J Clin Microbiol 37(7):2306–2311

    PubMed  Google Scholar 

  40. Cover TL, Glupczynski Y, Lage AP et al (1995) Serological detection of infection with CagA positive Helicobacter pylori strains. J Clin Microbiol 33:1496–1500

    PubMed  CAS  Google Scholar 

  41. Ogura K, Kanai F, Maeda S et al (1997) High prevalence of cytotoxin positive Helicobacter pylori in patients unrelated to the presence of peptic ulcers in Japan. Gut 41:463–468

    Article  PubMed  CAS  Google Scholar 

  42. Pan ZJ, vander Hulst RW, Feller M et al (1997) Equally high prevalence of infection with CagA positive Helicobacter pylori in Chinese patients with peptic ulcer disease and those with chronic gastritis associated dyspepsia. J Clin Microbiol 35:1344–1347

    PubMed  CAS  Google Scholar 

  43. Warzocha K, Salles G, Bienvenu J et al (1997) Tumor necrosis factor ligand-receptor system can predict treatment outcome in lymphoma patients. J Clin Oncol 15:499–508

    PubMed  CAS  Google Scholar 

  44. Matsumoto MS, Marianthasan HM, Nahm F et al (1996) Role of lymphotoxin and the type I TNF receptor in the formation of germinal centers. Science 271:1289–1291

    Article  PubMed  CAS  Google Scholar 

  45. Locksley RM, Killeen N, Lenardo MJ (2001) The TNF and TNF receptor superfamlies: integrating mammalian biology. Cell 104:487–501

    Article  PubMed  CAS  Google Scholar 

  46. Wu MS, Chen LT, Shun CT et al (2004) Promoter polymorphisms of tumor necrosis factor-alpha are associated with risk of gastric mucosa associated lymphoid tissue lymphoma. Int J Cancer 110:695–700

    Article  PubMed  CAS  Google Scholar 

  47. Hellmig S, Fischbach W, Elisabeth M et al (2005) A functional promotor polymorphism of TNF-a is associated with primary gastric B-cell lymphoma. Am J Gastroenterol 100:2644–2649

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

CSIR (New Delhi, India) is greatly acknowledged for providing fellowship to Mr. B.R. Achyut.

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Correspondence to Balraj Mittal.

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Achyut, B.R., Tripathi, P., Ghoshal, U.C. et al. Interleukin-10 (−819 C/T) and Tumor Necrosis Factor-α (−308 G/A) Gene Variants Influence Gastritis and Lymphoid Follicle Development. Dig Dis Sci 53, 622–629 (2008). https://doi.org/10.1007/s10620-007-9925-y

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  • DOI: https://doi.org/10.1007/s10620-007-9925-y

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