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
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
Dig Dis Sci. 2009 Nov;54(11):2391-8. doi: 10.1007/s10620-008-0624-0. Epub 2008 Dec 12.
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.
DNA甲基化是胃癌发生早期过程中的主要事件之一，它也发生在非肿瘤性胃黏膜中。亚甲基四氢叶酸还原酶（MTHFR）在叶酸生物转化形成S-腺苷甲硫氨酸（细胞中的通用甲基供体）过程中起核心作用，并影响DNA甲基化状态。我们研究了MTHFR C677T常见功能多态性与幽门螺杆菌感染的非肿瘤性胃黏膜中DNA甲基化状态之间的关联。对于99份来自幽门螺杆菌阳性非癌症受试者的胃黏膜样本，我们评估了MTHFR C677T基因多态性与四个候选启动子（p14、p16、死亡相关蛋白激酶和E-钙黏蛋白）的启动子甲基化状态之间的关联。在几乎所有受试者中，发现p16启动子甲基化与MTHFR 677T携带者之间存在弱相关性（年龄、性别校正后的比值比=2.57，P=0.053）。当根据年龄将受试者分为两组时，MTHFR T携带者发生p16启动子甲基化的风险显著更高，尤其是在66岁及以上人群中（性别校正后的比值比=14.28，P=0.02）。此外，在同一年龄段中，T携带者的甲基化CpG位点平均数量显著高于CC基因型（P=0.0418）。我们的数据表明，MTHFR 677T携带者在幽门螺杆菌感染的长期结果中影响胃黏膜DNA甲基化风险。
