Increased number of methylated CpG islands correlates with Helicobacter pylori infection, histological and serological severity of chronic gastritis

Tomomitsu Tahara, Tomiyasu Arisawa, Tomoyuki Shibata, Masakatsu Nakamura, Daisuke Yoshioka, Masaaki Okubo, Naoko Maruyama, Toshiaki Kamano, Yoshio Kamiya, Hiroshi Fujita, Yoshihito Nakagawa, Mitsuo Nagasaka, Masami Iwata, Kazuya Takahama, Makoto Watanabe, Hiromi Yamashita, Ichiro Hirata

研究成果: Article査読

31 被引用数 (Scopus)

抄録

Background Promoter hypermethylation of tumor suppressor genes is one of the major events in gastric carcinogenesis. Promoter hypermethylation is also present in non-neoplastic gastric epithelium as age-related phenomenon and some reports suggest the potential association between promoter hypermethylation and Helicobacter pylori infection. Here, we examined whether methylation of multiple promoter CpG islands would occur by H. pylori infection and correlate with histological or serological severity of chronic gastritis. Methods One hundred and ninety-one gastric mucosa samples were obtained by endoscopy. The promoter methylation status of the p14, p16, DAP-kinase and CDH1 genes were determined by methylation-specific- polymerase chain reaction. The degree of gastritis in the antrum was assessed according to the updated Sydney system in 150 participants. The pepsinogen (PG) l/ll ratio was calculated based on the data of serum PG I and PG II levels measured by radioimmunoassay in 54 selected cases. Results CpG island methylation was found in 32.5% for p14, 35.1% for p16, 43.5% for DAP-kinase and 36.1% for CDH1, whereas non, 1, 2, 3, and all methylation of four promoter CpG sites were present in 46 (24.1%), 59 (30.9%), 46 (24.1%), 30 (15.7%), and 10 (5.2%) participants, respectively. A strong association between the increased number of methylated CpG islands and H. pylori infection was observed (P< 0.0001). An increased number of methylated CpG islands was also associated with severity of neutrophil infiltration (P< 0.0001), mononuclear cell infiltration (P< 0.0001) and atrophy (P= 0.0021) in all, and severity of neutrophil infiltration (P= 0.0177) and mononuclear cell infiltration (P= 0.0004) in H. pylori- positive participants. An increased number of methylated CpG islands correlated with lower PG l/ll ratio in all (P= 0.0105) and H. py/or/'-infected participants (P= 0.074). Conclusion Multiple promoter CpG islands would be methylated by H. pylori infection, and an increased number of methylated CpG sites correlate with histological and serological severity of chronic gastritis.

本文言語English
ページ(範囲)613-619
ページ数7
ジャーナルEuropean Journal of Gastroenterology and Hepatology
21
6
DOI
出版ステータスPublished - 06-2009

All Science Journal Classification (ASJC) codes

  • 肝臓学
  • 消化器病学

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