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MTHFR 677T Carrier Influences the Methylation Status of H. Pylori-Infected Gastric Mucosa in Older Subjects

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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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Abbreviations

H. pylori :

Helicobacter pylori

MTHFR:

Methylenetetrahydrofolate reductase

MSP:

Methylation-specific-polymerase chain reaction

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Authors and Affiliations

  1. Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan

    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

  2. Department of Gastroenterology, Kanazawa Medical University, 1-1 Daigaku, Uchinadamachi, Ishikawa, 920-0293, Japan

    Tomiyasu Arisawa

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Correspondence to Tomomitsu Tahara.

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Tahara, T., Shibata, T., Nakamura, M. et al. MTHFR 677T Carrier Influences the Methylation Status of H. Pylori-Infected Gastric Mucosa in Older Subjects. Dig Dis Sci 54, 2391–2398 (2009). https://doi.org/10.1007/s10620-008-0624-0

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