title: Altered mucosal DNA methylation in parallel with highly active Helicobacter pylori-related gastritis.
abstract: BACKGROUND
  Chronic inflammation triggered by Helicobacter pylori causes altered DNA methylation in stomach mucosae, which is deeply involved in gastric carcinogenesis. This study aimed to elucidate the correlation between altered mucosal DNA methylation levels and activity of H. pylori-related gastritis, because inflammatory activity shows particular correlations with the development of diffuse-type cancer.
  
  
  METHODS
  Methylation levels in stomach mucosae of 78 healthy volunteers were determined by real-time methylation-specific PCR or bisulfite pyrosequencing. Examined loci were the promoter CpG islands of six genes (FLNc, HAND1, THBD, p41ARC, HRASLS, and LOX) and the CpG sites of non-coding repetitive elements (Alu and Satα) that are reportedly altered by H. pylori infection. Activity of H. pylori-related gastritis was evaluated using two serum markers: H. pylori antibody titer and pepsinogen II.
  
  
  RESULTS
  Methylation levels of the six CpG islands were consistently increased, and those of the two repetitive elements were consistently decreased in a stepwise manner with the activity of gastric inflammation as represented by serum marker levels. Each serum marker level was well correlated with the overall DNA methylation status of stomach mucosa, and these two serologic markers were additive in the detection of the mucosa with severely altered DNA methylation.
  
  
  CONCLUSIONS
  Alteration in mucosal DNA methylation level was closely correlated with activity of H. pylori-related gastritis as evaluated by serum markers. The observed correlation between altered DNA methylation levels and activity of H. pylori-related gastritis appears to be one of the relevant molecular mechanisms underlying the development of diffuse-type cancer.
authors.affiliation: Second Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, 641-0012, Japan, tayoshid@wakayama-med.ac.jp.
authors.forename: Takeichi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Jun
authors.initials: J
authors.lastname: Kato
authors.forename: Takao
authors.initials: T
authors.lastname: Maekita
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Shotaro
authors.initials: S
authors.lastname: Enomoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ando
authors.forename: Tohru
authors.initials: T
authors.lastname: Niwa
authors.forename: Hisanobu
authors.initials: H
authors.lastname: Deguchi
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ueda
authors.forename: Izumi
authors.initials: I
authors.lastname: Inoue
authors.forename: Mikitaka
authors.initials: M
authors.lastname: Iguchi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tamai
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ushijima
authors.forename: Masao
authors.initials: M
authors.lastname: Ichinose
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000097:blood / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins / Q000097:blood / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D064448:Filamins / Q000097:blood / Q000235:genetics; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology; D005756:Gastritis / Q000097:blood / Q000235:genetics* / Q000382:microbiology; D016481:Helicobacter Infections / Q000235:genetics* / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D010741:Phospholipases A; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics; D051127:Scavenger Receptors, Class E / Q000097:blood / Q000235:genetics; D013274:Stomach Neoplasms / Q000097:blood / Q000235:genetics* / Q000382:microbiology; D018180:Thrombomodulin / Q000097:blood / Q000235:genetics; D055815:Young Adult
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D064448:Filamins; D007074:Immunoglobulin G; D010741:Phospholipases A; D011506:Proteins; D051127:Scavenger Receptors, Class E; D018180:Thrombomodulin; C460821:ARPC1B protein, human; C578661:FLNC protein, human; C495137:OLR1 protein, human; C546931:THBD protein, human; C097341:helix-loop-helix protein, eHAND; C433809:PLAAT1 protein, human