Persistence of a component of DNA methylation in gastric mucosae after Helicobacter pylori eradication
Persistence of a component of DNA methylation in gastric mucosae after Helicobacter pylori eradication
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DOI：
10.1007/s00535-009-0142-7
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发表时间：
2010-01-01
影响因子：
6.3
通讯作者：
Ushijima, Toshikazu
中科院分区：
文献类型：
--
作者：
Nakajima, Takeshi;Enomoto, Shotaro;Ushijima, Toshikazu
幽门螺杆菌 (HP) 感染可有效诱导胃粘膜异常 DNA 甲基化，其积累与胃癌风险相关。甲基化水平（甲基化 DNA 分子的分数）的横断面分析和甲基化发生率的时间分析表明，HP 感染停止后甲基化水平下降。我们的目的是证明甲基化水平的下降。招募了 35 名接受过治愈性内镜切除术的 HP 感染患者和 11 名健康志愿者。通过实时甲基化特异性 PCR 定量甲基化水平。根据更新的悉尼系统进行组织学评估。在成功根除的 20 名患者中，FLNc 甲基化水平以及炎症细胞浸润在 6 周时从 0.6% 下降至 0.4%（P = 0.049），并在 1 年时保持较低水平。 THBD 甲基化水平 (30.1%) 在第 6 周时保持较高水平，但在第 1 年时下降至 19.0% (P = 0.0032)。成功根除的 9 名健康志愿者在 6 周时往往表现出 FLNc 和 THBD 下降。然而，降低后的甲基化水平仍然高于未感染HP的健康个体。在15名持续感染的患者中，甲基化水平保持不变。根除前，THBD甲基化水平与炎症细胞浸润程度相关（P < 0.05）。根除HP后，胃粘膜甲基化水平下降至一定水平，具有个体标志物特有的特征。建议慢性炎症参与甲基化诱导。
Helicobacter pylori (HP) infection potently induces aberrant DNA methylation in gastric mucosae, and its accumulation is associated with gastric cancer risk. Cross-sectional analysis of methylation levels (fraction of methylated DNA molecules) and temporal analysis of methylation incidence suggested that methylation levels decrease after HP infection discontinues. We aimed to demonstrate the decrease in methylation levels.Thirty-five patients with HP infection who had undergone curative endoscopic resection and 11 healthy volunteers were recruited. Methylation levels were quantified by real-time methylation-specific PCR. Histology was evaluated according to the updated Sydney System.In the 20 patients with successful eradication, the FLNc methylation level, along with infiltration of inflammatory cells, decreased from 0.6 to 0.4% at 6 weeks (P = 0.049) and remained low at 1 year. The THBD methylation level (30.1%) remained high at 6 weeks, but decreased to 19.0% at 1 year (P = 0.0032). Nine healthy volunteers with successful eradication tended to show a decrease of both FLNc and THBD at 6 weeks. However, the methylation levels after the decrease were still higher than those of healthy individuals without HP infection. In the 15 patients with persistent infection, the methylation levels remained the same. Before eradication, the THBD methylation level correlated with the degree of inflammatory cell infiltration (P < 0.05).Methylation levels in gastric mucosae decreased to certain levels after HP eradication in profiles unique to individual markers. Involvement of chronic inflammation in methylation induction was suggested.