2019 年第 8 期 第 14 卷

细胞色素P450 2C19基因多态性分型及其与急性冠状动脉综合征患者介入和抗血小板治疗后血小板高反应性的相关性

Relation between cytochrome P450 2C19 gene polymorphism and high on-treatment platelet reactivity after interventional and antiplatelet therapy in patients with acute coronary syndrome

作者：张素娟宋毓青魏明董茜吴其明程小艳

英文作者：

单位：100015首都医科大学附属北京地坛医院心内科（张素娟、宋毓青、魏明、董茜、吴其明）；100089北京市理化分析测试中心（程小艳）

英文单位：

关键词：急性冠状动脉综合征；细胞色素P4502C19基因多态性；血栓弹力图；治疗后血小板高反应性

英文关键词：

• 摘要：

• 【摘要】目的    探讨急性冠状动脉综合征（ACS）经皮冠状动脉介入治疗后给予阿司匹林、氯吡格雷双联抗血小板治疗患者细胞色素P450 2C19（CYP2C19）基因多态性分型及其与治疗后血小板高反应性（HTPR）等相关危险因素之间的相关性。方法    选择2017年1—12月在首都医科大学附属北京地坛医院确诊的ACS患者128例，均于经皮冠状动脉介入治疗后接受阿司匹林、氯吡格雷药物治疗。应用聚合酶链反应测序技术进行CYP2C19基因型检测，氯吡格雷快和超快代谢型患者为正常代谢组，中间代谢和慢代谢型为异常代谢组。比较2组患者的一般资料、凝血和生化指标水平和血小板反应性指标水平，分析CYP2C19不同基因型与血小板反应性的相关性。结果    正常代谢组共55例（43.0%），其中超快代谢型1例，快代谢型54例；异常代谢组共73例（57.0%），其中中间代谢型66例,慢代谢型7例。异常代谢组2型糖尿病比例高于正常代谢组［39.7%（29/73）比21.8%（12/55）］，差异有统计学意义（P＜0.05）；2组患者的性别、年龄和非ST段抬高型ACS、高血压、高脂血症、吸烟、陈旧脑梗死等既往病史，生化指标水平，以及2组患者血栓最大振幅、二磷酸腺苷诱导的血小板-纤维蛋白凝块强度、二磷酸腺苷抑制率和HTPR发生率比较差异均无统计学意义(均P＞0.05)。Pearson相关性分析结果表明，血小板低反应与CYP2C19基因多态性无显著相关性（r=-0.017，P=0.852）。结论    ACS携带CYP2C19基因中间代谢及慢代谢型组患者合并2型糖尿病比例高于快代谢和超快代谢型组。CYP2C19基因型与氯吡格雷HTPR之间无明显相关性。

• 【Abstract】Objective    To explore cytochrome P450(CYP)2C19 gene polymorphism in patients with acute coronary syndrome（ACS） and its correlation with high on-treatment platelet reactivity（HTPR） following aspirin plus clopidogrel antiplatelet therapy after percutaneous coronary intervention (PCI). Methods    A total of 128 patients diagnosed of ACS who underwent PCI from January to December 2017 in Beijing Ditan Hospital, Capital Medical University were enrolled. Routine antiplatelet therapy with aspirin and clopidogrel was performed after PCI. Polymorphisms of CYP2C19 gene were tested by polymerase chain reaction sequencing assay; patients with rapid and ultra-rapid metabolism of clopidogrel genotypes were included in normal metabolism group, while patients with intermediate and poor metabolism genotypes were abnormal metabolism group. General data, laboratory indicators of coagulation, biochemical test and platelet reactivity were recorded. The relation between CYP2C19 gene polymorphism and platelet reactivity was analyzed. Results    Among the 128 patients, 55 patients(43.0%) were normal metabolism genotypes including 1 case of ultra-rapid metabolism and 54 cases of rapid metabolism; 73 patients(57.0%) were abnormal metabolism genotypes including 66 cases of intermediate metabolism and 7 cases of poor metabolism. Comorbidity rate of type 2 diabetes mellitus in abnormal metabolism group was significantly higher than that in normal metabolism group［39.7%（29/73） vs 21.8%（12/55）］（P＜0.05）. There were no significant differences in gender, age, non-ST segment elevation ACS, hypertension, hyperlipidemia, smoking, old cerebral infarction, biochemical indicators, maximum amplitude of thrombus, adenosine diphosphate（ADP）-induced platelet-fibrin clot strength, ADP inhibition rate and HTPR incidence between normal and abnormal metabolism groups(all P＞0.05). Pearson analysis showed no significant correlation between low on-treatment platelet reactivity and CYP2C19 genotypes(r=-0.017，P=0.852）. Conclusions    ACS patients with intermediate and poor metabolism genotypes of CYP2C19 have a higher prevalence of type 2 diabetes mellitus. HTPR on clopidogrel after PCI is not associated with CYP2C19 gene polymorphism.