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

作者：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

来源：Digestive Diseases and Sciences, 2009, 54(11): 2391-2398.

DOI：10.1007/s10620-008-0624-0

• Methylation
• H. pylori
• Gastric mucosa
• MTHFR
• Polymorphism

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.

• 出版日期2009-11