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Altered mucosal DNA methylation in parallel with highly active Helicobacter pylori-related gastritis.
MedLine Citation:
PMID:  23292007     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Takeichi Yoshida; Jun Kato; Takao Maekita; Satoshi Yamashita; Shotaro Enomoto; Takayuki Ando; Tohru Niwa; Hisanobu Deguchi; Kazuki Ueda; Izumi Inoue; Mikitaka Iguchi; Hideyuki Tamai; Toshikazu Ushijima; Masao Ichinose
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-6
Journal Detail:
Title:  Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association     Volume:  -     ISSN:  1436-3291     ISO Abbreviation:  Gastric Cancer     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100886238     Medline TA:  Gastric Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Second Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, 641-0012, Japan, tayoshid@wakayama-med.ac.jp.
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