title: Methylation pattern of THBS1, GATA-4, and HIC1 in pediatric and adult patients infected with Helicobacter pylori.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Unidade Integrada de Farmacologia e Gastroenterologia, Universidade São Francisco, Av. São Francisco de Assis, 218. Jd. São José, Bragança Paulista, SP, Brazil.
authors.forename: Marisa Claudia
authors.initials: MC
authors.lastname: Alvarez
authors.forename: Marcelo Sady Placido
authors.initials: MS
authors.lastname: Ladeira
authors.forename: Isabel Cristina Affonso
authors.initials: IC
authors.lastname: Scaletsky
authors.forename: José
authors.initials: J
authors.lastname: Pedrazzoli
authors.forename: Marcelo Lima
authors.initials: ML
authors.lastname: Ribeiro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics*; D016481:Helicobacter Infections / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D012189:Retrospective Studies; D013270:Stomach / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000382:microbiology / Q000473:pathology; D019700:Thrombospondin 1 / Q000235:genetics*; D055815:Young Adult
chemical_list: D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; C499808:HIC1 protein, human; D051741:Kruppel-Like Transcription Factors; D019700:Thrombospondin 1