非瓣膜性心房颤动患者ABCB1和CES1基因多态性对达比加群酯抗凝疗效的影响  

Effects of ABCB1 and CES1 genetic polymorphisms on the anticoagulant efficacy of dabigatran etexilate in patients with non-valvular atrial fibrillation

作　　者：郑绪雅 张琳[1] 张俊峰[1] ZHENG Xuya;ZHANG Lin;ZHANG Junfeng(Department of Laboratory Medicine,the Fifth Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan;Academy of Medical Sciences of Zhengzhou University,Zhengzhou 450052,Henan,China)

机构地区：[1]郑州大学第五附属医院检验科,郑州450052 [2]郑州大学医学科学院,郑州450052

出　　处：《临床检验杂志》2021年第12期903-908,共6页Chinese Journal of Clinical Laboratory Science

摘　　要：目的探讨ABCB1 SNP rs1045642与CES1 SNP rs2244613基因多态性对非瓣膜性心房颤动患者服用达比加群酯的抗凝疗效的影响。方法选取2020年5月至2021年6月在郑州大学第五附属医院心内科住院的80例非瓣膜性心房颤动患者作为研究对象。检测患者ABCB1 SNP rs1045642与CES1 SNP rs2244613的基因型,测定患者服用达比加群酯后的血药浓度以及相关凝血指标,包括活化部分凝血活酶时间(APTT)和凝血酶时间(TT),并在患者治疗期间观察记录出血事件。分析ABCB1 SNP rs1045642与CES1 SNP rs2244613基因多态性对患者的达比加群血浆浓度、凝血指标和出血风险的影响。结果ABCB1 SNP rs1045642和CES1 SNP rs2244613的基因型分布均符合Hardy-Weinberg平衡(HWE)。ABCB1 SNP rs1045642与达比加群血浆浓度、凝血指标均无显著关联(P>0.05);此位点上不同基因型与房颤患者在治疗期间的出血事件发生率无关(P>0.05)。CES1 SNP rs2244613与达比加群峰浓度无显著性相关(P>0.05),对比达比加群的谷浓度,等位基因(C)携带者较非携带者显著降低(P<0.001);达比加群谷浓度时携带次要等位基因(C)的患者血浆APTT与TT的检测结果显著低于非携带次要等位基因(C)的患者(P<0.05);与非携带者相比,等位基因(C)携带者轻微出血的事件发生率显著降低(P<0.05)。结论ABCB1 SNP rs1045642基因位点的基因多态性可能不会影响房颤患者口服达比加群酯后的抗凝疗效。CES1 SNP rs2244613基因位点的多态性分析表明,携带次要等位基因(C)可以使服用达比加群酯治疗的房颤患者的血药浓度谷值及轻微出血风险降低。Objective To investigate the effects of ABCB1 SNP rs1045642 and CES1 SNP rs2244613 genetic polymorphisms on the anticoagulant efficacy of dabigatran etexilate in patients with non-valvular atrial fibrillation(NVAF).Methods Eighty patients with NVAF hospitalized in Department of Cardiology,the Fifth Affiliated Hospital of Zhengzhou University during May 2020 and June 2021 were enrolled in this study.The genotypes of ABCB1 SNP rs1045642 and CES1 SNP rs2244613 were detected.The plasma drug concentrations and related coagulation indexes such as activated partial thromboplastin time(APTT)and thrombin time(TT)were measured after dabigatran etexilate was taken by the patient.Meanwhile,the bleeding events were recorded during the treatment.The effects of ABCB1 SNP rs1045642 and CES1 SNP rs2244613 genetic polymorphisms on the plasma concentrations of dabigatran etexilate,coagulation indexes and bleeding risk of the patients were analyzed.Results The genotype distributions of ABCB1 SNP rs1045642 and CES1 SNP rs2244613 were consistent with Hardy-Weinberg equilibrium(HWE).ABCB1 SNP rs1045642 had no significant correlation with the plasma concentration of dabigatran etexilate and coagulation indexes(P>0.05),and different genotypes at this locus were not significantly correlated with the incidence of bleeding events during treatment in NVAF patients(P>0.05).There was no significant correlation between CES1 SNP rs2244613 and peak concentration of plasma dabigatran etexilate(P>0.05).The valley concentrations of plasma dabigatran etexilate in the carriers with allele C were significantly lower than that without allele C(P<0.001).During the valley concentrations of plasma dabigatran etexilate,the results of plasma APTT and TT in patients with minor allele C were significantly lower than that without minor allele C(P<0.05),and the incidence of minor bleeding events in the carriers with allele C was significantly lower than that without allele C(P<0.05).Conclusion The genetic polymorphism of ABCB1 SNP rs1045642 may not affect the an

关 键 词：达比加群酯 基因多态性 血浆浓度 抗凝治疗 非瓣膜性心房颤动 

分 类 号：R446[医药卫生—诊断学]