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

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)613-619
Number of pages7
JournalEuropean Journal of Gastroenterology and Hepatology
Volume21
Issue number6
DOIs
Publication statusPublished - 01-06-2009

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CpG Islands
Helicobacter Infections
Gastritis
Helicobacter pylori
Methylation
Pepsinogen A
Death-Associated Protein Kinases
Neutrophil Infiltration
Stomach
Pepsinogen C
Gastric Mucosa
Tumor Suppressor Genes
Endoscopy
Atrophy
Radioimmunoassay
Carcinogenesis
Epithelium
Polymerase Chain Reaction
Serum
Genes

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Tahara, Tomomitsu ; Arisawa, Tomiyasu ; Shibata, Tomoyuki ; Nakamura, Masakatsu ; Yoshioka, Daisuke ; Okubo, Masaaki ; Maruyama, Naoko ; Kamano, Toshiaki ; Kamiya, Yoshio ; Fujita, Hiroshi ; Nakagawa, Yoshihito ; Nagasaka, Mitsuo ; Iwata, Masami ; Takahama, Kazuya ; Watanabe, Makoto ; Yamashita, Hiromi ; Hirata, Ichiro. / Increased number of methylated CpG islands correlates with Helicobacter pylori infection, histological and serological severity of chronic gastritis. In: European Journal of Gastroenterology and Hepatology. 2009 ; Vol. 21, No. 6. pp. 613-619.
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abstract = "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.",
author = "Tomomitsu Tahara and Tomiyasu Arisawa and Tomoyuki Shibata and Masakatsu Nakamura and Daisuke Yoshioka and Masaaki Okubo and Naoko Maruyama and Toshiaki Kamano and Yoshio Kamiya and Hiroshi Fujita and Yoshihito Nakagawa and Mitsuo Nagasaka and Masami Iwata and Kazuya Takahama and Makoto Watanabe and Hiromi Yamashita and Ichiro Hirata",
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Tahara, T, Arisawa, T, Shibata, T, Nakamura, M, Yoshioka, D, Okubo, M, Maruyama, N, Kamano, T, Kamiya, Y, Fujita, H, Nakagawa, Y, Nagasaka, M, Iwata, M, Takahama, K, Watanabe, M, Yamashita, H & Hirata, I 2009, 'Increased number of methylated CpG islands correlates with Helicobacter pylori infection, histological and serological severity of chronic gastritis', European Journal of Gastroenterology and Hepatology, vol. 21, no. 6, pp. 613-619. https://doi.org/10.1097/MEG.0b013e32830e28b2

Increased number of methylated CpG islands correlates with Helicobacter pylori infection, histological and serological severity of chronic gastritis. / Tahara, Tomomitsu; Arisawa, Tomiyasu; Shibata, Tomoyuki; Nakamura, Masakatsu; Yoshioka, Daisuke; Okubo, Masaaki; Maruyama, Naoko; Kamano, Toshiaki; Kamiya, Yoshio; Fujita, Hiroshi; Nakagawa, Yoshihito; Nagasaka, Mitsuo; Iwata, Masami; Takahama, Kazuya; Watanabe, Makoto; Yamashita, Hiromi; Hirata, Ichiro.

In: European Journal of Gastroenterology and Hepatology, Vol. 21, No. 6, 01.06.2009, p. 613-619.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Increased number of methylated CpG islands correlates with Helicobacter pylori infection, histological and serological severity of chronic gastritis

AU - Tahara, Tomomitsu

AU - Arisawa, Tomiyasu

AU - Shibata, Tomoyuki

AU - Nakamura, Masakatsu

AU - Yoshioka, Daisuke

AU - Okubo, Masaaki

AU - Maruyama, Naoko

AU - Kamano, Toshiaki

AU - Kamiya, Yoshio

AU - Fujita, Hiroshi

AU - Nakagawa, Yoshihito

AU - Nagasaka, Mitsuo

AU - Iwata, Masami

AU - Takahama, Kazuya

AU - Watanabe, Makoto

AU - Yamashita, Hiromi

AU - Hirata, Ichiro

PY - 2009/6/1

Y1 - 2009/6/1

N2 - 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.

AB - 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.

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