Department of Gastroenterology, Kanazawa Medical University, Uchinadamachi, Kanazawa, Ishikawa, Japan.
Eur J Gastroenterol Hepatol. 2009 Jun;21(6):613-9. doi: 10.1097/MEG.0b013e32830e28b2.
Promoter hypermethylation of tumor suppressor genes is one of the major events in gastric carcinogenesis. Promoter hypermethylation is also present in non-neoplastic gastric epithelium as age-related phenomenon and some reports suggest the potential association between promoter hypermethylation and Helicobacter pylori infection. Here, we examined whether methylation of multiple promoter CpG islands would occur by H. pylori infection and correlate with histological or serological severity of chronic gastritis.
One hundred and ninety-one gastric mucosa samples were obtained by endoscopy. The promoter methylation status of the p14, p16, DAP-kinase and CDH1 genes were determined by methylation-specific-polymerase chain reaction. The degree of gastritis in the antrum was assessed according to the updated Sydney system in 150 participants. The pepsinogen (PG) I/II ratio was calculated based on the data of serum PG I and PG II levels measured by radioimmunoassay in 54 selected cases.
CpG island methylation was found in 32.5% for p14, 35.1% for p16, 43.5% for DAP-kinase and 36.1% for CDH1, whereas non, 1, 2, 3, and all methylation of four promoter CpG sites were present in 46 (24.1%), 59 (30.9%), 46 (24.1%), 30 (15.7%), and 10 (5.2%) participants, respectively. A strong association between the increased number of methylated CpG islands and H. pylori infection was observed (P<0.0001). An increased number of methylated CpG islands was also associated with severity of neutrophil infiltration (P<0.0001), mononuclear cell infiltration (P<0.0001) and atrophy (P=0.0021) in all, and severity of neutrophil infiltration (P=0.0177) and mononuclear cell infiltration (P=0.0004) in H. pylori-positive participants. An increased number of methylated CpG islands correlated with lower PG I/II ratio in all (P=0.0105) and H. pylori-infected participants (P=0.074).
Multiple promoter CpG islands would be methylated by H. pylori infection, and an increased number of methylated CpG sites correlate with histological and serological severity of chronic gastritis.
肿瘤抑制基因启动子的高甲基化是胃癌发生的主要事件之一。启动子高甲基化也是非肿瘤性胃上皮细胞的年龄相关现象，一些报告表明启动子高甲基化与幽门螺杆菌感染之间存在潜在的关联。在这里，我们研究了幽门螺杆菌感染是否会导致多个启动子 CpG 岛发生甲基化，并与慢性胃炎的组织学或血清学严重程度相关。
通过内镜获得 191 个胃黏膜样本。通过甲基化特异性聚合酶链反应确定 p14、p16、DAP-激酶和 CDH1 基因的启动子甲基化状态。根据 150 名参与者中更新的悉尼系统评估胃窦炎的程度。根据 54 例选择病例的血清 PG I 和 PG II 水平的放射免疫测定数据计算胃蛋白酶原（PG）I/II 比值。
p14 出现 CpG 岛甲基化的比例为 32.5%，p16 为 35.1%，DAP-激酶为 43.5%，CDH1 为 36.1%，而非甲基化、1 个甲基化、2 个甲基化、3 个甲基化和 4 个甲基化的比例分别为 46（24.1%）、59（30.9%）、46（24.1%）、30（15.7%）和 10（5.2%）。观察到增加的甲基化 CpG 岛数量与幽门螺杆菌感染之间存在很强的相关性（P<0.0001）。增加的甲基化 CpG 岛数量也与中性粒细胞浸润的严重程度相关（P<0.0001）、单核细胞浸润（P<0.0001）和萎缩（P=0.0021），在所有参与者中，与中性粒细胞浸润的严重程度（P=0.0177）和单核细胞浸润的严重程度（P=0.0004）相关。增加的甲基化 CpG 岛数量与所有参与者的 PG I/II 比值降低相关（P=0.0105）和幽门螺杆菌感染的参与者（P=0.074）。
幽门螺杆菌感染会导致多个启动子 CpG 岛发生甲基化，并且增加的甲基化 CpG 位点与慢性胃炎的组织学和血清学严重程度相关。
