基于microRNA的冠心病氯吡格雷低反应生物标志物研究  

Role of microRNA as the biomarkers of low-response to clopidogrel in patients with coronary heart disease

作　　者：高洁[1] 张莹[1] 官宝怡 史大卓[1] 马晓娟[1] GAO Jie;ZHANG Ying;GUAN Baoyi;SHI Dazhuo;MA Xiaojuan(Cardiovascular Disease Center,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China)

机构地区：[1]中国中医科学院西苑医院心血管病中心,北京市100091

出　　处：《中国动脉硬化杂志》2022年第2期135-140,共6页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金项目(81774141、81904046、82074418)。

摘　　要：目的探讨相关microRNA(miRNA)与冠心病氯吡格雷低反应的相关性及其作为生物标志物的诊断价值。方法筛选158例稳定型冠心病患者作为研究对象,采用光比浊法检测二磷酸腺苷(ADP)诱导的最大血小板聚集率(MPAR),将其中MPAR≥65%的35例患者纳入氯吡格雷低反应组(低反应组),并按年龄、性别配对将35例MPAR<65%的患者纳入氯吡格雷正常反应组(正常反应组)。采集患者外周血单核细胞并提取总RNA,利用实时荧光定量PCR技术检测miR-34a-5p、miR-370-3p、miR-432-5p和miR-495-3p在两组患者中的表达差异,并通过相关性分析和受试者工作特征(ROC)曲线分析评估差异miRNA对氯吡格雷低反应的诊断价值。结果与正常反应组相比,低反应组患者的miR-34a-5p和miR-495-3p表达显著升高,且差异倍数大于2(P<0.05);而miR-370-3p和miR-432-5p的表达差异不显著(P>0.05)。miR-34a-5p和miR-495-3p的表达与冠心病患者MPAR均呈显著正相关(r=0.709,P<0.01;r=0.597,P<0.01)。ROC曲线分析显示,miR-34a-5p诊断冠心病氯吡格雷低反应性的ROC曲线下面积为0.789,miR-495-3p的ROC曲线下面积为0.787,miR-34a-5p与miR-495-3p联合诊断的ROC曲线下面积为0.873,显著高于miR-34a-5p及miR-495-3p单一诊断(P<0.05)。结论miR-34a-5p和miR-495-3p的高表达均与冠心病氯吡格雷低反应性相关,有望成为诊断冠心病氯吡格雷低反应性的新型生物标志物。Aim To identify the correlation between microRNA(miRNA)and low-response to clopidogrel in patients with coronary heart disease(CHD),and explore their diagnostic value as biomarkers of low-response to clopidogrel.Methods 158 patients with stable CHD were recruited as the research population.The maximum platelet aggregation rate(MPAR)induced by adenosine diphosphate(ADP)was measured using light transmission aggregometry for all these patients.Eventually,35 patients of them whose MPAR≥65%were allocated to low-response group.For comparison,35 age-and gender-matched patients with MPAR<65%were allocated to normal-response group.The peripheral blood mononuclear cells(PBMC)were isolated from the blood samples of each patient to extract total RNA.The expression differences of miR-34a-5p,miR-370-3p,miR-432-5p and miR-495-3p in the two groups were detected by real-time quantitative PCR.The diagnostic value of differently expressed miRNA for low-response to clopidogrel were evaluated by correlation analysis and receiver-operating characteristic(ROC)curve analysis.Results Compared with normal-response group,the expressions of miR-34a-5p and miR-495-3p were significantly elevated in low-response group,and their fold changes were greater than 2(P<0.05).There was no significant difference in miR-370-3p and miR-432-5p expressions between two groups(P>0.05).The expressions of miR-34a-5p and miR-495-3p were positively correlated with MPAR in CHD patients(r=0.709,P<0.01;r=0.597,P<0.01).ROC curve analysis showed that the area under the curve(AUC)of miR-34a-5p was 0.789,and the AUC of miR-495-3p was 0.787;while the AUC of miR-34a-5p+miR-495-3p was 0.873,which was significantly higher than that of miR-34a-5p(P<0.05)or miR-495-3p(P<0.05).Conclusion Both the high expression of miR-34a-5p and miR-495-3p were associated with low-response to clopidogrel in CHD patients,and may serve as novel biomarkers for low-response to clopidogrel in CHD.

关 键 词：冠心病 氯吡格雷低反应 生物标志物 miR-34a-5p miR-495-3p 

分 类 号：R5[医药卫生—内科学]