Altered mucosal DNA methylation in parallel with highly active Helicobacter pylori-related gastritis
Altered mucosal DNA methylation in parallel with highly active Helicobacter pylori-related gastritis
复制标题
DOI：
10.1007/s10120-012-0230-x
复制
发表时间：
2013-10-01
期刊：
影响因子：
7.4
通讯作者：
Ichinose, Masao
中科院分区：
文献类型：
--
作者：
Yoshida, Takeichi;Kato, Jun;Ichinose, Masao
幽门螺杆菌引起的慢性炎症反应导致胃粘膜DNA甲基化改变，与胃癌的发生密切相关。本研究旨在阐明粘膜DNA甲基化水平改变与H。幽门相关性胃炎，因为炎症活动显示与弥漫型癌症的发展特别相关。检测的基因座是6个基因（FLNc、HAND1、THBD、p41ARC、HRASLS和LOX）的启动子CpG岛和非编码重复元件（Alu和Sat α）的CpG位点，据报道，这些基因被H.幽门感染H的活动。幽门螺杆菌相关性胃炎用两种血清标志物进行评估：H。pylori抗体滴度和胃蛋白酶原II。6个CpG岛的甲基化水平一致地增加，并且两个重复元件的甲基化水平一致地以逐步方式降低，其中以血清标志物水平表示的胃炎症活动。各血清标志物水平与胃粘膜DNA甲基化水平呈显著正相关，且在DNA甲基化水平严重改变的胃粘膜中，两种血清标志物具有相加作用，胃粘膜DNA甲基化水平的改变与H.幽门相关性胃炎的血清标志物评价。DNA甲基化水平的改变与H.幽门相关性胃炎似乎是弥漫型癌症发展的相关分子机制之一。
Chronic inflammation triggered by Helicobacter pylori causes altered DNA methylation in stomach mucosae, which is deeply involved in gastric carcinogenesis. This study aimed to elucidate the correlation between altered mucosal DNA methylation levels and activity of H. pylori-related gastritis, because inflammatory activity shows particular correlations with the development of diffuse-type cancer.Methylation levels in stomach mucosae of 78 healthy volunteers were determined by real-time methylation-specific PCR or bisulfite pyrosequencing. Examined loci were the promoter CpG islands of six genes (FLNc, HAND1, THBD, p41ARC, HRASLS, and LOX) and the CpG sites of non-coding repetitive elements (Alu and Sat alpha) that are reportedly altered by H. pylori infection. Activity of H. pylori-related gastritis was evaluated using two serum markers: H. pylori antibody titer and pepsinogen II.Methylation levels of the six CpG islands were consistently increased, and those of the two repetitive elements were consistently decreased in a stepwise manner with the activity of gastric inflammation as represented by serum marker levels. Each serum marker level was well correlated with the overall DNA methylation status of stomach mucosa, and these two serologic markers were additive in the detection of the mucosa with severely altered DNA methylation.Alteration in mucosal DNA methylation level was closely correlated with activity of H. pylori-related gastritis as evaluated by serum markers. The observed correlation between altered DNA methylation levels and activity of H. pylori-related gastritis appears to be one of the relevant molecular mechanisms underlying the development of diffuse-type cancer.