细胞色素P4502C19基因多态性对NSTE-ACS患者血小板反应性及临床预后的影响  

Effects of cytochrome P4502C19 gene polymorphism on platelet reactivity and clinical prognosis of patients with NSTE-ACS

作　　者：张莹莹[1] 郑君毅[1] 刘婷[1] 张莹[1] 马静[1] 刘寅[1] ZHANG Yingying;ZHENG Junyi;LIU Ting;ZHANG Ying;MA Jin;LIU Yin(Tianjin Chest Hospital,Tianjin 300222,China)

机构地区：[1]天津市胸科医院,天津市心血管病研究所,天津300222

出　　处：《山东医药》2020年第25期1-5,共5页Shandong Medical Journal

基　　金：天津市科技重大专项与工程项目(16ZXMJSY00150);天津市胸科医院院级基金项目(2018XKZ01)。

摘　　要：目的探讨细胞色素P4502C19(CYP2C19)基因多态性与非ST段抬高急性冠脉综合征(NSTE-ACS)患者服用氯吡格雷后血小板反应性的关系,并评价不同基因型对NSTE-ACS患者预后的影响。方法连续纳入接受PCI治疗的NSTE-ACS患者462例,依据CYP2C19基因型,分为快代谢型(CYP2C19*1/*1)、中间代谢型(CYP2C19*1/*2、CYP2C19*1/*3)和慢代谢型(CYP2C19*2/*2、CYP2C19*2/*3)。采用流式细胞术测定的血小板反应指数(PRI)和光比浊法测定的血小板聚集率(PAG)两种方法来评价患者在服用氯吡格雷后的血小板反应性。全部患者随访2年,以全因死亡、支架内再狭窄、急性支架内血栓形成、再发急性心肌梗死定义为主要不良心血管事件(MACE),采用Cox回归分析评价CYP2C19基因型、PRI、PAG等指标对MACE的预测能力。结果快代谢型158例、中间代谢型246例、慢代谢型58例。快代谢型、中间代谢型、慢代谢型PRI分别为48.6±10.5、56.7±12.6、65.3±11.4,PAG分别为67.4±8.5、71.9±8.2、78.4±6.1,三者两两比较P均<0.01。快代谢型、中间代谢型、慢代谢型MACE发生率分别为2.5%、9.8%、43.1%,三者两两比较P均<0.01。Cox回归分析显示,PRI(HR:1.05,95%CI:1.03~1.07,P<0.01)和CYP2C19基因型(HR:1.84,95%CI:1.09~3.12,P<0.05)为MACE的独立预测因子。结论CYP2C19基因型与NSTE-ACS患者服用氯吡格雷后的血小板反应性相关,慢代谢型可作为NSTE-ACS患者预后不良的预测指标。Objective To investigate the relationship between cytochrome P4502C19(CYP2C19)gene polymorphism and platelet reactivity in patients with non-ST-segment elevation acute coronary syndrome(NSTE-ACS)after clopidogrel administration,and to evaluate the prognostic value of the genotypes.Methods Totally 462 NSTE-ACS patients receiving PCI were successively included;according to the different genotypes of CYP2C19,they were divided into the extensive metabolism(EM)group(CYP2C19*1/*1),intermediate metabolism(IM)group(CYP2C19*1/*2,CYP2C19*1/*3)and poor metabolism(PM)group(CYP2C19*2/*2,CYP2C19*2/*3).Platelet reactivity after clopidogrel administration was evaluated by the platelet reactive index(PRI)measured by flow cytometry and platelet aggregation rate(PAG)measured by light transmittance aggregometry.All patients were followed up for 2 years;all-cause death,stent restenosis,acute stent thrombosis,and acute myocardial infarction were defined as major adverse cardiovascular events(MACE),and Cox regression analysis was performed to evaluate the predictive ability of genotypes,PRI,PAG,and other indicators on MACE.Results There were 158 cases of EM type,246 cases of IM type,and 58 cases of PM type.The PRI values were 48.6±10.5,56.7±12.6,and 65.3±11.4,respectively;the PAG were 67.4±8.5,71.9±8.2,and 78.4±6.1,respectively.There were statistical significant differences in PRI and PAG among the three groups(both P<0.01).The incidence rates of MACE in the three groups were 2.5%,9.8%and 43.1%,respectively.When we compared the three groups in pairs,statistical differences were found among them(P<0.01).Cox regression analysis indicated that PRI(HR:1.05,95%CI:1.03-1.07,P<0.01)and CYP2C19 genotypes(HR:1.84,95%CI:1.09-3.12,P<0.05)were independent predictors for MACE.Conclusion The CYP2C19 genotypes are associated with platelet reactivity of NSTE-ACS patients after clopidogrel administration,and PM genotype can be used as a prognostic indicator of poor prognosis in NSTE-ACS patients.

关 键 词：急性冠脉综合征 细胞色素P4502C19 基因多态性 血小板反应指数 主要不良心血管事件 

分 类 号：R541.4[医药卫生—心血管疾病]