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KCNQ1OT1、HIF1A-AS2 和 APOA1-AS 是冠心病诊断有前途的新型生物标志物。

KCNQ1OT1, HIF1A-AS2 and APOA1-AS are promising novel biomarkers for diagnosis of coronary artery disease.

机构信息

Institute for Translational Medicine, Qingdao University, Qingdao, China.

Affiliated Cardiovascular Hospital of Qingdao University, Qingdao University, Qingdao, China.

出版信息

Clin Exp Pharmacol Physiol. 2019 Jul;46(7):635-642. doi: 10.1111/1440-1681.13094. Epub 2019 Apr 29.

Abstract

This study aimed to evaluate the potential of long noncoding RNAs (lncRNAs) as biomarkers for coronary artery disease (CAD). We measured the levels of three atherosclerosis- or cardiac-related lncRNAs in peripheral blood monocyte cells (PBMCs) from 20 CAD patients and 20 non-CAD control participants using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) methods. We found that the levels of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), hypoxia-inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2) and apolipoprotein A-1 antisense RNA (APOA1-AS) were significantly increased in CAD patients (KCNQ1OT1 increased by 2.38-fold, P = 0.00042; HIF1A-AS2 increased by 2.00-fold, P = 0.0001; APOA1-AS increased by 4.52-fold, P = 0.000048). The area under the ROC curve was 0.865 for KCNQ1OT1, 0.852 for HIF1A-AS2, and 0.967 for APOA1-AS. Furthermore, the combination of lncRNAs resulted in a much higher AUC value of 0.990 for the prediction of CAD. Spearman's correlation analysis showed that APOA1-AS was positively correlated with NT-proBNP, CKMB, MYO and HsTnT, whereas HIF1A-AS2 was correlated with NT-proBNP and HsTnT. Hence, the elevation of KCNQ1OT1, HIF1A-AS2 and APOA1-AS predicts CAD and these molecules may be considered as novel biomarkers of CAD.

摘要

本研究旨在评估长非编码 RNA(lncRNA)作为冠心病(CAD)生物标志物的潜力。我们使用实时逆转录-聚合酶链反应(real-time RT-PCR)方法测量了 20 例 CAD 患者和 20 例非 CAD 对照参与者外周血单核细胞(PBMC)中三种动脉粥样硬化或心脏相关 lncRNA 的水平。我们发现,lncRNA KCNQ1 反义链/反义转录本 1(KCNQ1OT1)、缺氧诱导因子 1 ɑ 反义 RNA 2(HIF1A-AS2)和载脂蛋白 A-1 反义 RNA(APOA1-AS)在 CAD 患者中显著升高(KCNQ1OT1 增加 2.38 倍,P=0.00042;HIF1A-AS2 增加 2.00 倍,P=0.0001;APOA1-AS 增加 4.52 倍,P=0.000048)。KCNQ1OT1 的 ROC 曲线下面积为 0.865,HIF1A-AS2 为 0.852,APOA1-AS 为 0.967。此外,lncRNA 的联合预测 CAD 的 AUC 值更高,为 0.990。Spearman 相关性分析显示,APOA1-AS 与 NT-proBNP、CKMB、MYO 和 HsTnT 呈正相关,而 HIF1A-AS2 与 NT-proBNP 和 HsTnT 呈正相关。因此,KCNQ1OT1、HIF1A-AS2 和 APOA1-AS 的升高预测 CAD,这些分子可被视为 CAD 的新型生物标志物。

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