Department of Gastroenterology, Kanazawa Medical University, Uchinada‑machi, Ishikawa 920‑0293, Japan.
Department of Gastroenterology, Fujita Health University, Toyoake, Aichi 470‑1192, Japan.
Mol Med Rep. 2018 Aug;18(2):2381-2386. doi: 10.3892/mmr.2018.9200. Epub 2018 Jun 21.
The aim of the present study was to investigate an association of genetic polymorphism (rs7521584) located in miR‑200a‑200b‑429 cluster, which has tumor suppressor and pro‑inflammatory function, with the development of gastric mucosal atrophy and metaplasia as a pre‑malignant condition. Gastric mucosa samples were obtained from the antrum of 393 patients with no malignancies. The rs7521584 genotype was determined using the polymerase chain reaction‑single‑strand conformation polymorphism analysis method. The degree of gastritis was assessed histologically in all subjects and serum levels of pepsinogen (PG) I/II were quantified in 123 out of 393 patients. Patients with an atrophy score ≥1 and metaplasia score ≥1 were classified into the atrophic gastritis group (AG group). The rs7521584 TT genotype was significantly associated with the development of atrophic gastritis [odds ratio (OR), 2.41; 95% confidence interval (CI), 1.10‑5.25; P=0.027), particularly in patients with H. pylori infection (OR, 3.31; 95% CI, 1.35‑8.12; P=0.0089). In addition, in patients younger than 60 years of age, this genotype was associated with atrophic gastritis (OR, 3.15; 95% CI 1.03‑9.61; P=0.044)]. In patients with H. pylori infection, the metaplasia score was significantly higher in the TT homozygote compared with the GG+GT genotype. In the rs7521584 TT homozygote, serum PG I/II ratio was significantly reduced with increasing age (P=0.0084). No significant trend was identified between the GG+GT genotype and age. The results of the current study indicated that the rs7521584 minor allele homozygote was associated with the development of chronic gastritis under the influence of H. pylori‑induced inflammation, particularly with the severity of metaplastic alterations.
本研究旨在探讨位于 miR-200a-200b-429 簇中的遗传多态性（rs7521584）与胃黏膜萎缩和化生作为癌前状态的发展之间的关联。从 393 例无恶性肿瘤的患者的胃窦部获得胃黏膜样本。使用聚合酶链反应-单链构象多态性分析方法确定 rs7521584 基因型。所有受试者均进行组织学评估胃炎程度，在 393 例患者中的 123 例中定量检测胃蛋白酶原（PG）I/II 水平。将萎缩评分≥1 和化生评分≥1 的患者分为萎缩性胃炎组（AG 组）。rs7521584 TT 基因型与萎缩性胃炎的发生显著相关（比值比[OR]，2.41；95%置信区间[CI]，1.10-5.25；P=0.027），尤其是在幽门螺杆菌（H. pylori）感染的患者中（OR，3.31；95%CI，1.35-8.12；P=0.0089）。此外，在年龄小于 60 岁的患者中，该基因型与萎缩性胃炎相关（OR，3.15；95%CI，1.03-9.61；P=0.044）。在 H. pylori 感染的患者中，TT 纯合子的化生评分明显高于 GG+GT 基因型。在 rs7521584 TT 纯合子中，随着年龄的增加，血清 PG I/II 比值显著降低（P=0.0084）。在 GG+GT 基因型中，未发现与年龄之间存在显著趋势。本研究结果表明，在 H. pylori 诱导的炎症影响下，rs7521584 次要等位基因纯合子与慢性胃炎的发生有关，特别是与化生改变的严重程度有关。
