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目的:分析接受经皮冠状动脉介入治疗的冠心病患者CYP2C19基因突变情况及其对氯吡格雷抗血小板聚集的影响。方法:回顾性地选取2011年3月至2019年6月在南昌大学第二附属医院住院的冠心病患者，并选取同期遗传背景、性别、年龄与之相匹配的健康体检者作为对照。收集所有研究对象的基本临床资料及血液样本，提取DNA，采用Sanger一代测序法对冠心病患者及健康体检者行CYP2C19基因全外显子及外显子和内含子交界区测序以筛查CYP2C19基因变异。统计冠心病患者的基因变异发生率，并与千人基因组计划数据库和健康体检者的测序结果比较，以确定该基因变异是基因突变还是基因多态性。使用PolyPhen-2预测软件对基因突变进行有害性分析，以预测突变对蛋白功能的影响。在人正常肝脏细胞HL-7702中转染相同剂量的CYP2C19野生型质粒及筛查发现的CYP2C19基因突变质粒。转染24 h后，检测各组的CYP2C19蛋白酶表达量。将肝脏S9蛋白与氯吡格雷共孵育后作用于血小板，检测血小板聚集率和人血管舒张剂激活磷蛋白（VASP）活性。结果:共纳入1 493例冠心病患者和1 022名健康体检者，其中冠心病患者的年龄为（64.5±10.4）岁，男性1 129例（75.62%），健康体检者的年龄为（64.1±11.0）岁，男性778人（76.13%）。共在12例（0.80%）冠心病患者中共发现了5个CYP2C19基因突变，即4个已知突变T130K（1例）、M136K（6例）、N277K（3例）、V472I（1例）和一个新发突变G27V（1例），未在健康体检者中发现相应基因突变。T130K、M136K为很可能有害突变，G27V为可能有害突变，N277K和V472I为良性突变。体外研究发现，M136K基因突变组的血小板聚集率较野生型低24.83%（34.75%比59.58%，n P<0.05），磷酸化VASP水平比野生型高23.0%（1.23比1.00，n P0.05）。n 结论:在冠心病患者中共筛查出5个基因突变，即G27V、T130K、M136K、N277K、V472I。体外研究发现，CYP2C19基因突变M136K可增强CYP2C19蛋白酶对氯吡格雷的活化作用，进而抑制血小板聚集率，为功能获得型基因突变。“,”Objective:The purpose of this study was to investigate the effects of CYP2C19 gene mutations on clopidogrel antiplatelet activity in the patients with coronary heart disease treated by percutaneous coronary intervention.Methods:Patients with coronary heart disease, who hospitalized in the Second Affiliated Hospital of Nanchang University from March 2011 to June 2019, and healthy individuals with matching genetic background, gender, and age as controls were included in this study. Basic clinical data were analyzed and blood samples of all research subjects were obtained for extraction of DNA, and Sanger first-generation sequencing method was used to detect CYP2C19 gene mutation from full exon and exon and intron junction. CYP2C19 gene variations in patients with coronary heart disease were compared with the 1000 Genomes Browse database and the sequencing results of healthy controls to determine whether the gene variation was a genetic mutation or a genetic polymorphism. After that, PolyPhen-2 prediction software was used to analyze the harmfulness of gene mutations to predict the effect of mutations on protein function. The same dose of CYP2C19 wild-type plasmid and the CYP2C19 gene mutant plasmids were transfected into human normal liver cells HL-7702. After transfection of 24 h, the expression of CYP2C19 protease in each group was detected. The liver S9 protein was incubated with clopidogrel, acted on platelets to detect the platelet aggregation rate and the activity of human vasodilator-activated phosphoprotein (VASP).Results:A total of 1 493 patients with coronary heart disease (59.36%) were enrolled, the average age was (64.5±10.4) years old, of which 1 129 were male (75.62%). Meanwhile, 1 022 healthy physical examination volunteers (40.64%) were enrolled, and the average age was (64.1±11.0) years old, of which 778 were male (76.13%). A total of 5 gene mutations of CYP2C19 gene were identified in 12 patients (0.80%), namely, 4 known mutations T130K (1 case), M136K (6 cases), N277K (3 cases), V472I (1 case) and one new mutation G27V (1 case), no corresponding gene mutation was found in healthy controls. It was found that T130K and M136K were probably damaging, G27V was possibly damaging, and N277K and V472I were benign mutations. In vitro, we demonstrated that the platelet aggregation rate of the M136K gene mutation group was 24.83% lower than that of the wild type (59.58% vs.n 34.75%; n P<0.05), and the phosphorylated VASP level was 23.0% higher than that of the wild type (1.0 vs. 1.23;n P0.05).n Conclusions:In this study, 5 gene mutations are defined in patients with coronary heart disease, namely G27V, T130K, M136K, N277K, V472I. In vitro functional studies show that CYP2C19 gene mutation M136K, as a gain-of-function gene mutation, can enhance the activation of CYP2C19 enzyme on clopidogrel, thereby inhibiting the platelet aggregation rate.