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

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.