ATP结合盒转运蛋白B1与羧酸酯酶1基因多态性对达比加群酯药物谷浓度的影响

Effects of ABCB1 and CES1 Polymorphisms on Trough Concentrations of Dabigatran Etexilate

目的探讨ATP结合盒转运蛋白B1(ABCB1)及羧酸酯酶1(CES1)基因多态性与服用达比加群酯的患者药物谷浓度的相关性。方法选取2018年3月-2021年11月在福州某医院诊断为非瓣膜性房颤的69例患者作为研究对象。检测患者ABCB1及CES1的单核苷酸多态性位点以及基因型,采用抗Ⅱa因子显色法测定患者服用达比加群酯后药物的谷浓度,分析ABCB1及CES1基因多态性与谷浓度的相关性,进一步研究相关位点对谷浓度达标的影响。结果本研究共发现11个单核苷酸多态性位点,且ABCB1 rs2235013与ABCB1 rs2235033处于连锁不平衡状态(D’=0.96,r2=0.82)。但ABCB1基因多态性对达比加群谷浓度无显著影响(P>0.05)。CES1 rs2302719突变型(TG,GG)患者的达比加群谷浓度高于野生型(TT)(51.98±8.06 vs 42.44±3.88,57.71±9.06 vs 42.44±3.88),并且CES1 rs2302719突变型(TG,GG)是患者谷浓度达标的保护因素,结果具有统计学意义(P<0.05)。结论ABCB1基因多态性对达比加群谷浓度的影响还需进一步探索。CES1 rs2302719次要等位基因(G)可增加达比加群谷浓度,并且不良反应的发生率可能更低。

Objective To investigate the correlations of ATP binding cassette transporter B1(ABCB1)and carboxylesterase 1(CES1)polymorphisms with trough concentrations in patients taking dabigatran etexilate.Methods Sixty-nine patients with non-valvular atrial fibrillation hospitalized in the Department of Cardiology and Department of Neurology between March 2018 and November 2021 were enrolled in this study.The single nucleotide polymorphism(SNP)and genotypes of ABCB1 and CES1 of patients were detected.Meanwhile,the anti-Ⅱa activity was used to measure trough concentrations after dabigatran etexilate was taken.The correlations between ABCB1 and CES1 polymorphisms and trough concentrations were analyzed to find out whether the related SNPs could influence patients’ability to reach the standard trough concentration.Results A total of 11 SNPs were identified.ABCB1 rs2235013 and ABCB1 rs2235033 were in linkage disequilibrium(D'=0.96,r2=0.82).However,ABCB1 polymorphisms had no significant effect on trough concentrations of dabigatran(P>0.05).The trough concentration of CES1 rs2302719 mutants(TG,GG)was higher than that of wild-type(TT)(51.98±8.06 vs 42.44±3.88,57.71±9.06 vs 42.44±3.88).Moreover,CES1 rs2302719 mutants(TG,GG)were protective factors for patients to reach the standard trough concentration,and the results were statistically significant(P<0.05).Conclusion The effect of ABCB1 polymorphisms on the trough concentration of dabigatran needs to be further explored.The minor allele(G)of CES1 rs2302719 can increase the trough concentration of dabigatran,and the incidence of adverse events may be lower.