Methylation pattern of THBS1, GATA-4, and HIC1 in pediatric and adult patients infected with Helicobacter pylori

Dig Dis Sci. 2013 Oct;58(10):2850-7. doi: 10.1007/s10620-013-2742-6. Epub 2013 Jun 14.

Abstract

Background: Helicobacter pylori infection is usually acquired in childhood and persists into adulthood if untreated. The bacterium induces a chronic inflammatory response, which is associated with epigenetic alterations in oncogenes, tumor-suppressor genes, cell-cycle regulators, and cell-adhesion molecules.

Aim: The aim of this study was to analyze the effect of H. pylori infection on the methylation status of Thrombospondin-1 (THBS1), Hypermethylated in cancer 1 (HIC1) and Gata binding protein-4 (GATA-4) in gastric biopsy samples from children and adults infected or uninfected with the bacterium and in samples obtained from gastric cancer patients.

Methods: The methylation pattern was analyzed with methylation-specific PCR.

Results: Our results showed that H. pylori infection was associated with methylation of the promoter regions of the THBS1 and GATA-4 genes in pediatric and adult samples (p < 0.01). HIC1 showed the lowest level of methylation, which was not an early event during gastric carcinogenesis.

Conclusions: The results from this study indicate that methylation of THBS1 and GATA-4 occurs in the early stages of chronic gastritis and gastric cancer in association with H. pylori infection; however, in gastric cancer samples, other mechanisms cooperate with the down-regulation of these genes. Methylation of HIC1 may not be the principal mechanism implicated in its down-regulation in gastric cancer samples.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Child
  • Child, Preschool
  • DNA Methylation / physiology*
  • Down-Regulation
  • Female
  • GATA4 Transcription Factor / genetics*
  • Helicobacter Infections / physiopathology*
  • Helicobacter pylori / isolation & purification
  • Helicobacter pylori / physiology*
  • Humans
  • Kruppel-Like Transcription Factors / genetics*
  • Male
  • Middle Aged
  • Promoter Regions, Genetic / genetics
  • Retrospective Studies
  • Stomach / microbiology
  • Stomach / pathology
  • Stomach Neoplasms / microbiology
  • Stomach Neoplasms / pathology
  • Thrombospondin 1 / genetics*
  • Young Adult

Substances

  • GATA4 Transcription Factor
  • GATA4 protein, human
  • HIC1 protein, human
  • Kruppel-Like Transcription Factors
  • Thrombospondin 1