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CYP2C19*2基因多态性与经皮冠状动脉介入治疗后氯吡格雷抗血小板临床疗效的相关性 被引量:9

Relationship between CYP2C19*2 genetic polymorphism and clinical outcomes in patients treated with clopidogrel during antiplatelet therapy after percutaneous coronary intervention
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摘要 目的探讨CYP2C19*2(c.681G〉A,rs4244285)基因多态性与经皮冠状动脉介入(percutaneouscoronaryintervention,PCI)治疗后氯吡格雷抗血小板临床疗效的相关性。方法选择478例接受PCI治疗的急性冠脉综合征(acutecoronarysyndrome,ACS)患者,采用TaqMan基因分型技术检测其CYP2C19*2的基因多态性。患者术后均采用氯吡格雷抗血小板治疗并定期随访,分析不同基因型与PCI治疗后支架内血栓、主要心血管事件(majoradversecardiacevents,MACE)发生率及生存时间的相关性。采用COX单因素分析检测PCI治疗后发生MACE的相关因素,采用COX多因素分析检测PCI治疗后MACE的危险因素。结果本研究人群中的CYP2C19*2的基因型分布符合Hardy—Weinberg平衡。478例患者纯合野生型(GG)238例(49.8%),杂合型(GA)加纯合突变型(AA)240例(50.2%)。分析结果显示,对于支架内血栓(P=0.025)及MACE(P=0.09),携带681GG基因型的患者预后较携带681A等位基因(AA/AG基因型)的好。单因素COX回归结果显示,CYP2C19*2的基因型、糖尿病病史、原发性高血压(高血压)病史[RR(95%CI)为2.796(1.245—6.281)、2.157(1.039—4.478)和3.564(1.364-9.312)]是发生MACE的相关因素。多因素COX回归分析结果显示,CYP2C19*2的基因型、高血压病史是发生MACE的危险因素。结论CYP2C19*2的基因多态性与PCI治疗后氯吡格雷抗血小板临床疗效有关,CYP2C19*2基因突变能够降低氯吡格雷抗血小板效果,增加PCI治疗后发生支架内血栓、MACE的风险。 Objectives To study the relationship between CYP2C19 * 2 (c.681G〉A, rs4244285) genetic polymorphism and clinical outcomes in patients treated with clopidogrel during antiplatelet therapy after percutaneous coronary intervention (PCI). Methods Totally 478 patients with acute coronary syndrome (ACS) who received PCI were selected and polymorphisms of CYP2C19 * 2 gene were detected by TaqMan gene analysis techniques. All the patients were treated with clopidogrel during antiplatelet therapy after PCI and followed up regularly. Statistical analysis was conducted to investigate the association among gene polymorphism, stent thrombosis, major adverse cardiac events (MACE) andsurvival time. Correlation factors of MACE were analyzed by single factor COX regression analysis and risk factors of MACE were analyzed by multiple factor COX regression analysis. Results The genotype distribution was found to be with Hardy-Weinberg equilibrium in the study. In the 478 patients,238 (49.8%) patients were homozygous wild-type (GG), and 240 (50.2%) patients were heterozygous mutant (AG) and homozygous mutant (AA). Analysis showed that patients with 681GG genotype had a better prognosis on stcnt thrombosis (P=0.025) and MACE (P=0.09) than patients with 681A allele (AA/AG genotype). Univariate COX regression showed that polymorphism,diabetes mellitus and hypertension [RR (95%CI) : 2.796 ( 1.245-6.281 ), 2.157 (1.039-4.478), 3.564 (1.364-9.312) ] were correlation factors of MACE, and multivariate COX regression showed that polymorphism and hypertension were risk factors of MACE. Conclusions CYP2C19 * 2 genetic polymorphism is associated with clinical outcomes in patients treated with clopidogrel during antiplatelet therapy after PCI. Mutation of CYP2C19 * 2 gene can decrease the drug action of clopidogrel during antiplatelet therapy and increase the risk of stent thrombosis and MACE.
出处 《岭南心血管病杂志》 2014年第3期275-279,289,共6页 South China Journal of Cardiovascular Diseases
基金 国家自然科学基金(项目编号:81072701) 广东省自然科学基金(项目编号:10151008002000002) 广东省人民医院引进学科带头人启动基金(项目编号:Y022009127) 广东省科技计划项目(项目编号:2009B030801256)
关键词 冠状动脉疾病 CYP2C19 基因多态性 血管成形术 经腔 经皮冠状动脉 氯吡格雷 抗血小板 支架内血栓 主要心血管事件 coronary artery disease CYP2C 19 genetic polymorphism percutaneous coronary intervention clopidogrel antiplatelet stent thrombosis major adverse cardiac events
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