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循环miR-221、miR-130a和miR-155对冠心病的预测作用:中国多民族研究

Predictive Effects of Circulating miR-221, miR-130a and miR-155 for Coronary Heart Disease: A Multi-Ethnic Study in China.

作者信息

Jia Qiao-Wei, Chen Zhao-Hong, Ding Xiao-Qing, Liu Jie-Yin, Ge Peng-Cheng, An Feng-Hui, Li Li-Hua, Wang Lian-Sheng, Ma Wen-Zhu, Yang Zhi-Jian, Jia En-Zhi

机构信息

Department of Cardiovascular Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Cardiovascular Medicine, the Friendship Hospital of Ili Kazakh Autonomous Prefecture, Yining, China.

出版信息

Cell Physiol Biochem. 2017;42(2):808-823. doi: 10.1159/000478071. Epub 2017 Jun 19.

Abstract

BACKGROUND

Differences in microRNA (miRNA) profiles between patients with and without coronary heart disease (CHD)have not been fully determined. The purpose of the study was to evaluate in a multi-ethnic population in China the predictive value of miRNAs previously suggested to have a role in CHD.

SUBJECT AND METHOD

932 participants were included, and plasma samples obtained. A quantitative reverse-transcription PCR(RT-qPCR) assay was conducted to confirm the concentration of plasma miRNAs. Circulating levels of miRNAs were quantified using the 2-Δct method. The severity of coronary atherosclerosis was evaluated via Gensini Scores.

RESULT

The circulating levels of the nine proposed miRNAs were not different among the five main ethnicities examined (all p > 0.05). The Spearman correlation analyses indicated that miR-221 and miR-130a were negatively associated with the severity of CHD as indicated by Gensini Scores (r = -0.106, p = 0.001;r = -0.073, p = 0.026). Results of the univariate analysis showed that lower circulating miR-221 (OR, 1.663; 95 % CI, 1.255-2.202, p = <0.001), miR-155 (OR, 1.520; 95 % CI, 1.132-2.042, p = 0.005), and miR-130a (OR, 1.943; 95% CI, 1.410-2.678, p = <0.001) were potential risk factors for CHD. Moreover, miR-130a (OR, 2.405; 95 % CI, 1.691-3.421, p = <0.001) remained independently associated with the risk of CHD after adjusting for potential confounding factors. The analysis of the possible positive/negative associations between miR-221, miR-155 and miR-130awere conducted. A positive association between miR-130a and miR-155 was found (SI = 1.60, SIM = 1.21 and AP = 0.22), and in these groups, the proportion of CHD attributable to the interaction between miR-130a and miR-155 was as high as 22 %. A negative interaction was found between miR-221 and miR-130a (SI = 0.68, SIM = 0.60 and AP = 0.27).

CONCLUSION

Plasma levels of miR-221, miR-130a and miR-155 decreased in patients with CHD, and miR-130a may be an independent predictor for CHD.

摘要

背景

冠心病(CHD)患者与非冠心病患者之间的微小RNA(miRNA)谱差异尚未完全明确。本研究的目的是在中国的多民族人群中评估先前提示在冠心病中起作用的miRNA的预测价值。

对象与方法

纳入932名参与者,并采集血浆样本。采用定量逆转录聚合酶链反应(RT-qPCR)检测法确定血浆miRNA的浓度。使用2-Δct法对循环miRNA水平进行定量。通过Gensini评分评估冠状动脉粥样硬化的严重程度。

结果

在所检测的五个主要民族中,所提出的9种miRNA的循环水平无差异(所有p>0.05)。Spearman相关性分析表明,miR-221和miR-130a与Gensini评分所提示的冠心病严重程度呈负相关(r=-0.106,p=0.001;r=-0.073,p=0.026)。单因素分析结果显示,循环miR-221水平较低(OR,1.663;95%CI,1.255-2.202,p<0.001)、miR-155(OR,1.520;95%CI,1.132-2.042,p=0.005)和miR-130a(OR,1.943;95%CI,1.410-2.678,p<0.001)是冠心病的潜在危险因素。此外,在校正潜在混杂因素后,miR-130a(OR,2.405;95%CI,1.691-3.421,p<0.001)仍与冠心病风险独立相关。对miR-221、miR-155和miR-130a之间可能的正/负关联进行了分析。发现miR-130a与miR-155之间存在正相关(SI=1.60,SIM=1.21,AP=0.22),在这些组中,miR-130a与miR-155相互作用导致的冠心病比例高达22%。发现miR-221与miR-130a之间存在负相互作用(SI=0.68,SIM=0.60,AP=0.27)。

结论

冠心病患者血浆miR-221、miR-130a和miR-155水平降低,且miR-130a可能是冠心病的独立预测因子。

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