"The impact of ABCB1, CYP3A4/5 and ABCG2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non-valvular atrial fibrillation"

作者全名："Wu, Tingting; Wu, Shuyi; Li, Li; Xiang, Jing; Wang, Na; Chen, Wenjun; Zhang, Jinhua"

作者地址："[Wu, Tingting; Wu, Shuyi; Chen, Wenjun; Zhang, Jinhua] Fujian Med Univ, Fujian Matern & Child Hlth Hosp, Coll Clin Med Obstet & Gynecol & Pediat, Dept Pharm, 18 Daoshan Rd, Fuzhou 350001, Peoples R China; [Li, Li] Guizhou Prov Peoples Hosp, Dept Pharm, Guiyang, Peoples R China; [Xiang, Jing; Wang, Na] Chongqing Med Univ, Affiliated Hosp 2, Dept Pharm, Chongqing, Peoples R China"

通信作者："Zhang, JH (通讯作者)，Fujian Med Univ, Fujian Matern & Child Hlth Hosp, Coll Clin Med Obstet & Gynecol & Pediat, Dept Pharm, 18 Daoshan Rd, Fuzhou 350001, Peoples R China."

来源：HUMAN GENOMICS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001024982000001

JCR分区：Q2

影响因子：3.8

年份：2023

卷号：17

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Rivaroxaban; Gene polymorphisms; Pharmacokinetics; Bleeding; Non-valvular atrial fibrillation

摘要："BackgroundThe influence of genetic factors on the pharmacokinetics and clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) is poorly understood. This study aimed to explore the effects of CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms on the trough concentrations and the bleeding risk of rivaroxaban in NVAF patients.Patients and methodsThis study is a prospective multicenter study. The patient's blood samples were collected to detect the steady-state trough concentrations of rivaroxaban and gene polymorphisms. We visited the patients regularly at month 1, 3, 6, and 12 to record bleeding events and medications.ResultsA total of 95 patients were enrolled in this study, and 9 gene loci were detected. For the dose-adjusted trough concentration ratio (C-trough/D) of rivaroxaban, the homozygous mutant type was significantly lower than wild type at ABCB1 rs4148738 locus (TT vs. CC, P = 0.033), and the mutant type was significantly lower than the wild type at ABCB1 rs4728709 locus (AA + GA vs. GG, P = 0.008). ABCB1 (rs1045642, rs1128503), CYP3A4 (rs2242480, rs4646437), CYP3A5 (rs776746), and ABCG2 (rs2231137, rs2231142) gene polymorphisms had no significant effect on the C-trough/D of rivaroxaban. For the bleeding events, we found that there were no significant differences among genotypes of all gene loci.ConclusionThis study found for the first time that ABCB1 rs4148738 and rs4728709 gene polymorphisms had a significant impact on the C-trough/D of rivaroxaban in NVAF patients. CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms were not associated with the bleeding risk of rivaroxaban."

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