CYP2C19、PEAR1和PON1基因多态性与抗血小板聚集功能及预后的关系

Association of CYP2C19, PEAR1 and PON1 gene polymorphisms with antiplatelet aggregation function and prognosis

目的:探究冠心病患者CYP2C19、PEAR1和PON1基因多态性与抗血小板聚集功能及临床预后的相关性。方法:纳入2018年3月至2020年10月于安徽医科大学附属省立医院心内科进行治疗的186例冠心病患者,均给予氯吡格雷及阿司匹林治疗,根据血小板聚集率将患者分为高反应组及低反应组,根据患者治疗1年后主要心血管不良事件发生情况将患者分为预后较好组及预后不良组,分析氯吡格雷代谢基因多态性与血小板聚集功能及预后的关系。结果:高反应组CYP2C19 rs681、PEAR1和PON1 rs108突变型检出率均高于低反应组,联合检测评估血小板聚集功能的AUC大于PEAR1和PON1基因单独检测(P<0.05);预后不良组的CYP2C19 rs681、PEAR1和PON1 rs108突变型检出率高于预后较好组(P<0.05);联合检测预测冠心病患者预后的曲线下面积(AUC)大于PON1 rs108基因单独检测(P<0.05);CYP2C19 rs681、PEAR1基因突变型是影响冠心病患者预后的危险因素(P<0.05)。结论:冠心病患者CYP2C19 rs681、PEAR1和PON1 rs108基因多态性联合检测对血小板聚集功能及预后具有评估价值,且与双抗治疗相关的血小板聚集功能及预后相关。

OBJECTIVE To explore the correlation between polymorphisms of gene metabolism and clopidogrel antiplatelet aggregation function, clinical prognosis in patients with coronary heart disease(CHD).METHODS A total of 186 patients with CHD treated with clopidogrel and aspirin in cardiology department of The Affiliated Provincial Hospital of Anhui Medical University were enrolled between March 2018 and October 2020. The genotypes of cytochrome P450(CYP) 2 C19 at rs681 locus, platelet endothelial aggregation receptor 1(PEAR1) and paraoxonase 1(PON1) at rs108 locus were detected. According to platelet aggregation rate, they were divided into high-response group and low-response group. According to the occurrence of major cardiovascular adverse events after one year of treatment, they were divided into good prognosis group and poor prognosis group. The relationship between polymorphisms of clopidogrel metabolic genes and platelet aggregation function, prognosis was analyzed.RESULTS The detection rates of CYP2 C19 rs681, PEAR1 and PON1 rs108 mutations in high-response group were higher than those in low-response group(P<0.05). AUC of combined detection for assessing platelet aggregation function was greater than that of PEAR1 and PON1 alone(P<0.05). The detection rates of CYP2 C19 rs681, PEAR1 and PON1 rs108 mutations in poor prognosis group were higher than those in good prognosis group(P<0.05). AUC of combined detection for predicting the prognosis of CHD patients was greater than that of PON1 rs108 alone(P<0.05). CYP2 C19 rs681 and PEAR1 mutations were risk factors for prognosis in CHD patients(P<0.05).CONCLUSION The combined detection of CYP2 C19 rs681, PEAR1 and PON1 rs108 gene polymorphisms in patients with coronary heart disease has value in evaluating platelet aggregation function and prognosis, and is related to platelet aggregation function and prognosis after dual antiplatelet therapy.