Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China.
PLoS One. 2013 Apr 17;8(4):e61250. doi: 10.1371/journal.pone.0061250. Print 2013.
MicroRNAs (miRNAs) have been implicated in various human diseases. Single nucleotide polymorphisms (SNPs) in inflammation-related miRNA may play an important role in Helicobacter pylori (H. pylori)-induced gastric lesions. To evaluate the associations between miRNA SNPs, H. pylori and gastric lesions, a population-based study was conducted in Linqu County, China.
METHODOLOGY/PRINCIPAL FINDINGS: Based on serum miRNA array conducted in this population, two SNP loci (miR-146a rs2910164: G>C and miR-27a rs895819: T>C) were determined by polymerase chain reaction-restriction fragment length polymorphism in 2,380 participants with diverse gastric lesions. Using participants with superficial gastritis and mild chronic atrophic gastritis as the reference group, we found that rs2910164 CC carriers had a significantly increased risk of intestinal metaplasia [adjusted odds ratio (OR), 1.42; 95% confidence interval (CI), 1.03-1.97] and dysplasia (OR, 1.54; 95% CI, 1.05-2.25) compared to GG carriers, whereas no significant association was observed for rs895819. Stratified analysis by H. pylori infection indicated that rs2910164 C allele was associated with an increased risk of intestinal metaplasia and dysplasia only among individuals infected with H. pylori (CC vs. GG: OR, 1.53; 95% CI, 1.12-2.08, P for trend = 0.004). Participants who simultaneously carried variant alleles and H. pylori infection were more likely to develop intestinal metaplasia and dysplasia, although the interaction between genetic variants and H. pylori infection was not significant (P for interaction = 0.35 for rs2910164 and 0.92 for rs895819).
CONCLUSIONS/SIGNIFICANCE: These findings suggest that miR-146a rs2910164 polymorphism may contribute to the evolution of H. pylori-associated gastric lesions in this high-risk population.
微小 RNA（miRNAs）参与了多种人类疾病。炎症相关 miRNA 的单核苷酸多态性（SNP）可能在幽门螺杆菌（H. pylori）诱导的胃病变中发挥重要作用。为了评估 miRNA SNP、H. pylori 和胃病变之间的关系，在中国临朐县进行了一项基于人群的研究。
方法/主要发现：基于该人群进行的血清 miRNA 芯片，通过聚合酶链反应-限制性片段长度多态性在 2380 名具有不同胃病变的参与者中确定了两个 SNP 位点（miR-146a rs2910164：G>C 和 miR-27a rs895819：T>C）。以浅表性胃炎和轻度慢性萎缩性胃炎患者为参考组，我们发现 rs2910164 CC 携带者发生肠化生的风险显著增加[校正优势比（OR），1.42；95%置信区间（CI），1.03-1.97]和发育不良（OR，1.54；95% CI，1.05-2.25）与 GG 携带者相比，而 rs895819 则无明显相关性。按 H. pylori 感染分层分析表明，rs2910164 C 等位基因仅与 H. pylori 感染个体的肠化生和发育不良风险增加相关（CC 与 GG：OR，1.53；95%CI，1.12-2.08，P 趋势=0.004）。同时携带变异等位基因和 H. pylori 感染的参与者更有可能发生肠化生和发育不良，尽管遗传变异和 H. pylori 感染之间的相互作用不显著（rs2910164 的 P 交互=0.35，rs895819 的 P 交互=0.92）。
结论/意义：这些发现表明，miR-146a rs2910164 多态性可能导致高危人群中 H. pylori 相关胃病变的发生。
