MTHFR 677T carrier influences the methylation status of H. pylori-infected gastric mucosa in older subjects

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

DNA methylation is one of the major events in the early process of gastric carcinogenesis and it also occurs in non-neoplastic gastric mucosa. MTHFR plays a central role in biotransformation of folate to form S-adenosylmethionine, the universal methyl donor in cells and affects DNA methylation status. We investigated the association between common functional polymorphism of MTHFR C677T and DNA methylation status in H. pylori-infected non-neoplastic gastric mucosa. For 99 gastric mucosa samples from H. pylori positive non-cancer subjects, we assessed the association between MTHFR C677T genetic polymorphism and promoter methylation status of the four candidate promoters (p14, p16, DAP-kinase, and CDH1). In most all of the subjects, weak correlation was found between the p16 promoter methylation and MTHFR 677T carriers (age, sex-adjusted OR = 2.57, P = 0.053). When subjects were divided into two groups according to age, the MTHFR T carrier held a significantly higher risk of p16 promoter methylation, especially in 66 years or older generation (sex-adjusted OR = 14.28, P = 0.02). In addition, mean number of methylated CpG cites were significantly higher in T carrier than CC genotype in the same generation (P = 0.0418). Our data suggest that MTHFR 677T carrier influences the risk of DNA methylation in gastric mucosa in the long-term outcome of the H. pylori infection.

Original languageEnglish
Pages (from-to)2391-2398
Number of pages8
JournalDigestive Diseases and Sciences
Volume54
Issue number11
DOIs
Publication statusPublished - 01-11-2009

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Pylorus
DNA Methylation
Gastric Mucosa
Methylation
Death-Associated Protein Kinases
S-Adenosylmethionine
Genetic Polymorphisms
Biotransformation
Folic Acid
Genetic Promoter Regions
Stomach
Carcinogenesis
Genotype
Infection

All Science Journal Classification (ASJC) codes

  • Physiology
  • Gastroenterology

Cite this

Tahara, Tomomitsu ; Shibata, Tomoyuki ; Nakamura, Masakatsu ; Yamashita, Hiromi ; Yoshioka, Daisuke ; Okubo, Masaaki ; Maruyama, Naoko ; Kamano, Toshiaki ; Kamiya, Yoshio ; Fujita, Hiroshi ; Nakagawa, Yoshihito ; Nagasaka, Mitsuo ; Iwata, Masami ; Takahama, Kazuya ; Watanabe, Makoto ; Hirata, Ichiro ; Arisawa, Tomiyasu. / MTHFR 677T carrier influences the methylation status of H. pylori-infected gastric mucosa in older subjects. In: Digestive Diseases and Sciences. 2009 ; Vol. 54, No. 11. pp. 2391-2398.
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abstract = "DNA methylation is one of the major events in the early process of gastric carcinogenesis and it also occurs in non-neoplastic gastric mucosa. MTHFR plays a central role in biotransformation of folate to form S-adenosylmethionine, the universal methyl donor in cells and affects DNA methylation status. We investigated the association between common functional polymorphism of MTHFR C677T and DNA methylation status in H. pylori-infected non-neoplastic gastric mucosa. For 99 gastric mucosa samples from H. pylori positive non-cancer subjects, we assessed the association between MTHFR C677T genetic polymorphism and promoter methylation status of the four candidate promoters (p14, p16, DAP-kinase, and CDH1). In most all of the subjects, weak correlation was found between the p16 promoter methylation and MTHFR 677T carriers (age, sex-adjusted OR = 2.57, P = 0.053). When subjects were divided into two groups according to age, the MTHFR T carrier held a significantly higher risk of p16 promoter methylation, especially in 66 years or older generation (sex-adjusted OR = 14.28, P = 0.02). In addition, mean number of methylated CpG cites were significantly higher in T carrier than CC genotype in the same generation (P = 0.0418). Our data suggest that MTHFR 677T carrier influences the risk of DNA methylation in gastric mucosa in the long-term outcome of the H. pylori infection.",
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Tahara, T, Shibata, T, Nakamura, M, Yamashita, H, Yoshioka, D, Okubo, M, Maruyama, N, Kamano, T, Kamiya, Y, Fujita, H, Nakagawa, Y, Nagasaka, M, Iwata, M, Takahama, K, Watanabe, M, Hirata, I & Arisawa, T 2009, 'MTHFR 677T carrier influences the methylation status of H. pylori-infected gastric mucosa in older subjects', Digestive Diseases and Sciences, vol. 54, no. 11, pp. 2391-2398. https://doi.org/10.1007/s10620-008-0624-0

MTHFR 677T carrier influences the methylation status of H. pylori-infected gastric mucosa in older subjects. / Tahara, Tomomitsu; Shibata, Tomoyuki; Nakamura, Masakatsu; Yamashita, Hiromi; Yoshioka, Daisuke; Okubo, Masaaki; Maruyama, Naoko; Kamano, Toshiaki; Kamiya, Yoshio; Fujita, Hiroshi; Nakagawa, Yoshihito; Nagasaka, Mitsuo; Iwata, Masami; Takahama, Kazuya; Watanabe, Makoto; Hirata, Ichiro; Arisawa, Tomiyasu.

In: Digestive Diseases and Sciences, Vol. 54, No. 11, 01.11.2009, p. 2391-2398.

Research output: Contribution to journalArticle

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T1 - MTHFR 677T carrier influences the methylation status of H. pylori-infected gastric mucosa in older subjects

AU - Tahara, Tomomitsu

AU - Shibata, Tomoyuki

AU - Nakamura, Masakatsu

AU - Yamashita, Hiromi

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 - Hirata, Ichiro

AU - Arisawa, Tomiyasu

PY - 2009/11/1

Y1 - 2009/11/1

N2 - DNA methylation is one of the major events in the early process of gastric carcinogenesis and it also occurs in non-neoplastic gastric mucosa. MTHFR plays a central role in biotransformation of folate to form S-adenosylmethionine, the universal methyl donor in cells and affects DNA methylation status. We investigated the association between common functional polymorphism of MTHFR C677T and DNA methylation status in H. pylori-infected non-neoplastic gastric mucosa. For 99 gastric mucosa samples from H. pylori positive non-cancer subjects, we assessed the association between MTHFR C677T genetic polymorphism and promoter methylation status of the four candidate promoters (p14, p16, DAP-kinase, and CDH1). In most all of the subjects, weak correlation was found between the p16 promoter methylation and MTHFR 677T carriers (age, sex-adjusted OR = 2.57, P = 0.053). When subjects were divided into two groups according to age, the MTHFR T carrier held a significantly higher risk of p16 promoter methylation, especially in 66 years or older generation (sex-adjusted OR = 14.28, P = 0.02). In addition, mean number of methylated CpG cites were significantly higher in T carrier than CC genotype in the same generation (P = 0.0418). Our data suggest that MTHFR 677T carrier influences the risk of DNA methylation in gastric mucosa in the long-term outcome of the H. pylori infection.

AB - DNA methylation is one of the major events in the early process of gastric carcinogenesis and it also occurs in non-neoplastic gastric mucosa. MTHFR plays a central role in biotransformation of folate to form S-adenosylmethionine, the universal methyl donor in cells and affects DNA methylation status. We investigated the association between common functional polymorphism of MTHFR C677T and DNA methylation status in H. pylori-infected non-neoplastic gastric mucosa. For 99 gastric mucosa samples from H. pylori positive non-cancer subjects, we assessed the association between MTHFR C677T genetic polymorphism and promoter methylation status of the four candidate promoters (p14, p16, DAP-kinase, and CDH1). In most all of the subjects, weak correlation was found between the p16 promoter methylation and MTHFR 677T carriers (age, sex-adjusted OR = 2.57, P = 0.053). When subjects were divided into two groups according to age, the MTHFR T carrier held a significantly higher risk of p16 promoter methylation, especially in 66 years or older generation (sex-adjusted OR = 14.28, P = 0.02). In addition, mean number of methylated CpG cites were significantly higher in T carrier than CC genotype in the same generation (P = 0.0418). Our data suggest that MTHFR 677T carrier influences the risk of DNA methylation in gastric mucosa in the long-term outcome of the H. pylori infection.

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