Wang Yan, Chen Min, Chen Hui, Wang Fang
Department of Cardiovascular Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Laboratory of Cardiology, Beijing Hospital, National Center of Gerontology, Beijing, China.
Front Pharmacol. 2021 Apr 14;12:639854. doi: 10.3389/fphar.2021.639854. eCollection 2021.
Genetic data on the pharmacokinetics of rivaroxaban and identification of factors that affect its biotransformation, distribution, and excretion will allow for generation of algorithms for personalized use of this drug in patients with atrial fibrillation (AF). Here we tested the effects of (ATP-binding cassette subfamily B member 1) polymorphisms on the valley rivaroxaban blood concentration and on the frequency of hemorrhagic events in patients with AF and propose a personal anticoagulation therapy management protocol. This is a retrospective study. We enrolled Mongolian descent patients who met the criteria from May 2018 to August 2019 in Beijing and Fujian. Clinical data on gender, height, weight, liver and kidney functions, drug trough concentration, and drug dosage were collected; we recorded the bleeding events until 6 months after initiating the medication. single nucleotide polymorphisms including rs1128503, rs1045642, and rs4148738 were identified. After reaching the steady state of plasma concentration, the peripheral blood was collected to detect the trough rivaroxaban plasma concentrations before the next medication. We included 155 patients in this study including 81 men and 74 women, with an average age of 71.98 ± 10.72 years. The distribution of genotypes conformed to the Hardy-Weinberg equilibrium. Multiple comparisons between wild (TT) and mutant (CT and CC) genotypes at the rs1045642 locus showed no significant differences of rivaroxaban trough concentrations (TT vs. CT, = 0.586; TT vs. CC, = 0.802; and CT vs. CC, = 0.702). Multiple comparison between wild (TT) and mutant (CC) genotypes at the rs1128503 locus revealed a significant difference of rivaroxaban trough concentrations (TT vs. CC, = 0.0421). But wild (TT) vs mutant (CT) genotypes and mutant CT vs mutant CC genotypes at the rs1128503 locus showed no significant differences of rivaroxaban trough concentrations (TT vs. CT, = 0.0651; TT vs. CT, = 0.6127). Multiple comparisons between wild (GG) and mutant (AG and AA) genotypes at the rs4148738 locus showed no significant differences of rivaroxaban trough concentrations (GG vs. AG, = 0.341; GG vs. AA, = 0.612; AG vs. AA, = 0.649). There was no significant correlation between ABCB1 gene variation loci rs1045642, rs1128503, rs4148738 and bleeding events. rs1128503 locus variations are correlated with the serum concentration of rivaroxaban in patients of Mongolian descent. But no significant correlation between rs1128503 locus variations and bleeding events were obtained.
利伐沙班药代动力学的遗传数据以及对影响其生物转化、分布和排泄因素的识别，将有助于生成在心房颤动（AF）患者中个性化使用该药物的算法。在此，我们测试了ABCB1（ATP结合盒转运体B家族成员1）基因多态性对AF患者利伐沙班血药谷浓度及出血事件发生频率的影响，并提出了个性化抗凝治疗管理方案。这是一项回顾性研究。我们纳入了2018年5月至2019年8月在北京和福建符合标准的蒙古族后裔患者。收集了性别、身高、体重、肝肾功能、药物谷浓度和药物剂量等临床数据；我们记录了开始用药后6个月内的出血事件。识别出包括rs1128503、rs1045642和rs4148738在内的单核苷酸多态性。在血浆浓度达到稳态后，采集外周血以检测下次用药前利伐沙班血浆谷浓度。本研究共纳入155例患者，其中男性81例，女性74例，平均年龄为71.98±10.72岁。ABCB1基因型分布符合Hardy-Weinberg平衡。rs1045642位点野生型（TT）与突变型（CT和CC）基因型之间的多重比较显示，利伐沙班谷浓度无显著差异（TT vs. CT，P = 0.586；TT vs. CC，P = 0.802；CT vs. CC，P = 0.702）。rs1128503位点野生型（TT）与突变型（CC）基因型之间的多重比较显示，利伐沙班谷浓度有显著差异（TT vs. CC，P = 0.0421）。但rs1128503位点野生型（TT）与突变型（CT）基因型以及突变型CT与突变型CC基因型之间，利伐沙班谷浓度无显著差异（TT vs. CT，P = 0.0651；CT vs. CC，P = 0.6127）。rs4148738位点野生型（GG）与突变型（AG和AA）基因型之间的多重比较显示，利伐沙班谷浓度无显著差异（GG vs. AG，P = 0.341；GG vs. AA，P = 0.612；AG vs. AA，P = 0.649）。ABCB1基因变异位点rs1045642、rs1128503、rs4148738与出血事件之间无显著相关性。rs1128503位点变异与蒙古族后裔患者利伐沙班血清浓度相关。但未获得rs1128503位点变异与出血事件之间的显著相关性。
