摘要
目的:探究血小板内皮聚集受体-1(PEAR1)基因多态性对服用阿司匹林和氯吡格雷的急性冠脉综合征(ACS)患者的血小板反应性以及预后的影响。方法:连续纳入某院心内科的207例ACS患者,服用阿司匹林和氯吡格雷维持治疗1年。对患者进行基因分型,并根据连锁不平衡系数和基因分布频率进行单倍型分析,使用血栓弹力图仪(TEG)检测患者的血小板抑制率,观察1年间的心源性死亡、非致死性心肌梗死、靶血管血运重建、心绞痛复发等缺血事件,同时观察了出血事件。结果:将rs12566888、rs12041331、rs2644592、rs822442、rs822441和rs4661012这6个紧密连锁的单核苷酸多态性(SNP)分为5个常见的单倍型,按照TEG法检测的血小板抑制率(PIR)从高到低排序定义为H1~H5,将H1作为对照组比较其他组与血小板反应性及终点结局的相关性。单倍型H4(占13.61%)与H5(占10.99%)相比于H1来说与血小板抑制率的降低显著相关(P值分别为0.042;0.044)。rs11264579与其他SNP之间连锁关系弱(r^2<0.3),该位点突变与缺血事件(OR:0.46,95%CI:0.23~0.94,P=0.032)以及靶血管血运重建(OR:0.26,95%CI:0.07~0.93,P=0.038)的发生风险降低显著相关。结论:对于服用阿司匹林和氯吡格雷的ACS患者来说,PEAR1基因单倍型H4、H5与血小板抑制率降低显著相关,rs11264579突变与临床结局的改善显著相关,但本研究在血小板抑制率与临床结局之间没有找到必然的联系。
OBJECTIVE To study the correlation between platelet endothelial aggregation receptor-1（PEAR1）polymorphisms and platelet reactivity,clinical outcomes in acute coronary syndrome（ACS）patients treated with antiplatelet drugs.METHODS Totally 207 ACS patients treated with aspirin and clopidogrel for 1 year were enrolled.Genotype and haplotype of PEAR1 were analyzed,platelet reactivity was tested by thromboelastogram（TEG）.During 1-year follow up,ischemic events were recorded,including cardiac death,nonfatal myocardial infarction,target vessels revascularization,unstable angina.Bleeding events were also recorded.RESULTS Five haplotypes were inferred from six of the selected PEAR1 SNPs,which then were classified into H1-H5 by platelet inhibition rate（PIR）in descending order tested using TEG.PIR decreased significantly in H4 and H5 haplotypes compared with H1（P=0.041;P=0.044,respectively）.The polymorphism of rs11264579,which had weak relationship with other SNPs,was associated with the decreased risk of ischemic events（OR：0.46,95% CI：0.23-0.94,P=0.032）and target vessels revascularization（OR：0.26,95% CI：0.07-0.93,P=0.038）.CONCLUSION For ACS patients taking aspirin and clopidogrel,the H4 and H5 haplotypes are associated with the PIR.The rs11264579 polymorphism is associated with better clinical outcomes.However,there seems no relationship between PIR and clinical outcomes in our study.
作者
李俊蕾
梁广楷
覃思蓓
扶宇
聂小燕
史录文
邵宏
刘健
LI Jun-lei;LIANG Guang-kai;QIN Si-bei;FU Yu;NIE Xiao-yan;SHI Lu-wen;SHAO Hong;LIU Jian(Department of Pharmacy Administration and Clinical Pharmacy,School of Pharmaceutical Sciences,Peking University Health Science Center, Beijing 100191, China;Department of Cardiology, Peking University People＇ s Hospital, Beijing 100044, China)
出处
《中国医院药学杂志》
CAS
北大核心
2018年第6期640-644,共5页
Chinese Journal of Hospital Pharmacy
基金
北京高等学校"青年英才计划"项目(编号:YETP0064)
