血小板源性 miR-126 的功能基因多态性与急性冠状动脉综合征患者氯吡格雷抗血小板反应性及疗效的相关性

Correlation of functional gene polymorphism of platelet-derived miR-126 with antiplatelet reactivity of clopidogrel and outcome in acute coronary syndrome patients

摘要:

目的 分析血小板源性miR-126 的功能基因多态性rs4636297与急性冠状动脉综合征(ACS)患者氯吡格雷抗血小板反应性及疗效的相关性。方法 连续募集 2015 年11月至 2017 年2月在解放军总医院第一医学中心心血管内科住院期间接受氯吡格雷联合阿司匹林双联抗血小板治疗,同时在稳定抗栓治疗第3天接受血小板反应性检测的ACS患者。提取患者外周全血DNA并进行miR-126的功能基因多态性rs4636297的基因检测。对所有患者进行1年随访,主要监测缺血事件发生情况。采用SPSS 22.0统计软件进行数据分析。通过logistic回归分析与氯吡格雷抗血小板反应性以及1年内主要缺血终点事件相关的独立影响因素。结果 入选364例经氯吡格雷和阿司匹林双联抗血小板治疗的 ACS 患者,根据血小板反应性检测结果,193 例入选血小板高反应性(HTPR)组,171 例入选血小板低反应性(LTPR)组。经多因素校正分析后,HTPR 组携带rs4636297 A等位基因的比例仍明显高于LTPR组(OR=1.85,95%CI:1.162.96;P =0.010)；通过1年随访观察发现,A等位基因携带者发生主要缺血终点事件的风险明显高于非携带者(OR=4.09,95%CI:1.25,13.35;P=0.020)。结论 血小板源性miR-126的功能基因多态性rs4636297可能影响ACS患者氯吡格雷抗血小板治疗的反应性及疗效。

Abstract:

Objective To analyze the correlation of genetic polymorphism of miR-126 rs4636297 derived from platelet with anti-platelet reactivity of clopidogrel and clinical outcome in patients with acute coronary syndrome (ACS). Methods Consecutive ACS patients who were treated with clopidogrel and aspirin and underwent platelet reactivity test in 3d after stable antithrombotic therapy in Department of Cardiology, First Medical Center, Chinese PLA General Hospital from November 2015 to February 2017 were recruited in the study. Their peripheral blood samples were harvested to extract DNA to detect the polymorphism of miR-126 rs4636297. All patients were followed up for primary ischemic events within 1 year from discharging. SPSS statistics 22.0 was used for data analysis. Logistic regression analysis was used to study the independent influencing factors related to antiplatelet reactivity of clopidogrel and primary ischemic events within 1 year. Results A total of 364 patients were enrolled finally, and 193 of them were assigned into high on-treatment platelet reactivity (HTPR) group and the other 171 into the low on-treatment platelet reactivity (LTPR) group according to the results of platelet reactivity test. After adjustment, multivariate analysis indicated that the proportion of rs4636297 A allele was significantly larger in the HTPR group than the LTPR group (OR=1.85,95%CI:1.16-2.96; P=0.010). In the 1-year follow-up observation, the risk of primary ischemic events was obviously higher in the A allele carriers than the non-carriers (OR=4.09,95%CI:1.25-13.35; P=0.020). Conclusion The functional gene polymorphism rs4636297 of platelet-derived miR-126 may affect the response and outcome of clopidogrel antiplatelet therapy in ACS patients.