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前体微小RNA-146a中的一个基因变异(rs2910164 C>G)与中国人群急性冠状动脉综合征风险降低相关。

A Genetic Variant in Pre-miR-146a (rs2910164 C>G) Is Associated with the Decreased Risk of Acute Coronary Syndrome in a Chinese Population.

作者信息

Huang Suli, Lv Ziquan, Deng Qifei, Li Lu, Yang Binyao, Feng Jing, Wu Tangchun, Zhang Xiaomin, Cheng Jinquan

机构信息

Shenzhen Center for Disease Control and Prevention.

出版信息

Tohoku J Exp Med. 2015 Nov;237(3):227-33. doi: 10.1620/tjem.237.227.

Abstract

MicroRNAs (miRNAs) can contribute to the development of cardiovascular diseases, and single nucleotide polymorphisms (SNPs) in miRNA genes may influence disease susceptibility by altering mature miRNA expression levels. However, the effect of SNPs located in miR-146a and miR-196a2 genes on risk of acute coronary syndrome (ACS) has not been reported in the Chinese population. Two miRNA polymorphisms located in miRNA genes (miR-146a rs2910164 C>G and miR-196a2 rs11614913 T>C) were genotyped in 722 ACS patients and 721 control subjects. The CG genotype of rs2910164 was significantly associated with decreased risk of ACS [CG vs. CC, odds ratio (OR) = 0.72, 95% confidence interval (CI): 0.55-0.95, P = 0.020; dominant model, OR = 0.77, 95% CI: 0.60-0.99, P = 0.044]. We did not find any association of rs11614913 with the risk of ACS. Stratification analysis showed that the rs2910164 CG genotype was associated with decreased risk of ACS (dominant model) in males, subjects with body mass index more than 24 kg/m(2), and in hypertensive subjects. Significant combined effects were also observed between rs2910164 and blood lipids or C-reactive protein levels. In summary, this study provides the first evidence that the CG genotype of miR-146a rs2910164 is associated with a significantly decreased risk of ACS in a Chinese population. Moreover, rs2910164 and blood lipids or an inflammatory marker may have a combined effect on the onset of ACS. These findings indicate that miR-146a rs2910164 may act as a novel molecular marker for ACS susceptibility.

摘要

微小RNA(miRNA)可促使心血管疾病的发生发展,而miRNA基因中的单核苷酸多态性(SNP)可能通过改变成熟miRNA的表达水平影响疾病易感性。然而,在中国人群中,位于miR - 146a和miR - 196a2基因的SNP对急性冠状动脉综合征(ACS)风险的影响尚未见报道。我们对722例ACS患者和721例对照者进行了位于miRNA基因中的两个miRNA多态性(miR - 146a rs2910164 C>G和miR - 196a2 rs11614913 T>C)的基因分型。rs2910164的CG基因型与ACS风险降低显著相关[CG与CC相比,比值比(OR)=0.72,95%置信区间(CI):0.55 - 0.95,P = 0.020;显性模型,OR = 0.77,95% CI:0.60 - 0.99,P = 0.044]。我们未发现rs11614913与ACS风险存在任何关联。分层分析显示,rs2910164的CG基因型与男性、体重指数超过24 kg/m²的受试者以及高血压受试者的ACS风险降低相关(显性模型)。在rs2910164与血脂或C反应蛋白水平之间也观察到显著的联合效应。总之,本研究首次提供证据表明,在中国人群中,miR - 146a rs2910164的CG基因型与ACS风险显著降低相关。此外,rs2910164与血脂或炎症标志物可能对ACS的发病具有联合作用。这些发现表明,miR - 146a rs2910164可能作为ACS易感性的新型分子标志物。

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