The impact of ABCB1, CYP3A4/5 and ABCG2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non-valvular atrial fibrillation
Abstract Background The 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 conc...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Human Genomics |
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| Online Access: | https://doi.org/10.1186/s40246-023-00506-3 |
| _version_ | 1797784525932068864 |
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| author | Tingting Wu Shuyi Wu Li Li Jing Xiang Na Wang Wenjun Chen Jinhua Zhang |
| author_facet | Tingting Wu Shuyi Wu Li Li Jing Xiang Na Wang Wenjun Chen Jinhua Zhang |
| author_sort | Tingting Wu |
| collection | DOAJ |
| description | Abstract Background The 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 methods This 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. Results A total of 95 patients were enrolled in this study, and 9 gene loci were detected. For the dose-adjusted trough concentration ratio (Ctrough/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 Ctrough/D of rivaroxaban. For the bleeding events, we found that there were no significant differences among genotypes of all gene loci. Conclusion This study found for the first time that ABCB1 rs4148738 and rs4728709 gene polymorphisms had a significant impact on the Ctrough/D of rivaroxaban in NVAF patients. CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms were not associated with the bleeding risk of rivaroxaban. |
| first_indexed | 2024-03-13T00:41:09Z |
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| id | doaj.art-ede2677ab94b4c36b43ad0638bb09412 |
| institution | Directory Open Access Journal |
| issn | 1479-7364 |
| language | English |
| last_indexed | 2024-03-13T00:41:09Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
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| series | Human Genomics |
| spelling | doaj.art-ede2677ab94b4c36b43ad0638bb094122023-07-09T11:19:28ZengBMCHuman Genomics1479-73642023-07-011711810.1186/s40246-023-00506-3The impact of ABCB1, CYP3A4/5 and ABCG2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non-valvular atrial fibrillationTingting Wu0Shuyi Wu1Li Li2Jing Xiang3Na Wang4Wenjun Chen5Jinhua Zhang6Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical UniversityDepartment of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical UniversityDepartment of Pharmacy, Guizhou Provincial People’s HospitalDepartment of Pharmacy, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Pharmacy, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical UniversityDepartment of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical UniversityAbstract Background The 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 methods This 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. Results A total of 95 patients were enrolled in this study, and 9 gene loci were detected. For the dose-adjusted trough concentration ratio (Ctrough/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 Ctrough/D of rivaroxaban. For the bleeding events, we found that there were no significant differences among genotypes of all gene loci. Conclusion This study found for the first time that ABCB1 rs4148738 and rs4728709 gene polymorphisms had a significant impact on the Ctrough/D of rivaroxaban in NVAF patients. CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms were not associated with the bleeding risk of rivaroxaban.https://doi.org/10.1186/s40246-023-00506-3RivaroxabanGene polymorphismsPharmacokineticsBleedingNon-valvular atrial fibrillation |
| spellingShingle | Tingting Wu Shuyi Wu Li Li Jing Xiang Na Wang Wenjun Chen Jinhua Zhang The impact of ABCB1, CYP3A4/5 and ABCG2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non-valvular atrial fibrillation Human Genomics Rivaroxaban Gene polymorphisms Pharmacokinetics Bleeding Non-valvular atrial fibrillation |
| title | The impact of ABCB1, CYP3A4/5 and ABCG2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non-valvular atrial fibrillation |
| title_full | The impact of ABCB1, CYP3A4/5 and ABCG2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non-valvular atrial fibrillation |
| title_fullStr | The impact of ABCB1, CYP3A4/5 and ABCG2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non-valvular atrial fibrillation |
| title_full_unstemmed | The impact of ABCB1, CYP3A4/5 and ABCG2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non-valvular atrial fibrillation |
| title_short | The impact of ABCB1, CYP3A4/5 and ABCG2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non-valvular atrial fibrillation |
| title_sort | impact of abcb1 cyp3a4 5 and abcg2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non valvular atrial fibrillation |
| topic | Rivaroxaban Gene polymorphisms Pharmacokinetics Bleeding Non-valvular atrial fibrillation |
| url | https://doi.org/10.1186/s40246-023-00506-3 |
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