Influence of ABCB1, CYP3A5 and CYP3A4 gene polymorphisms on prothrombin time and the residual equilibrium concentration of rivaroxaban in patients with non-valvular atrial fibrillation in real clinical practice.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2022-12-01 DOI:10.1097/FPC.0000000000000483

Dmitry Alekseevitch Sychev, Aleksey Vladimirovich Sokolov, Olga Vilorovna Reshetko, Vladimir Petrovich Fisenko, Igor Nikolaevich Sychev, Elena Anatolievna Grishina, Pavel Olegovich Bochkov, Roman Vladimirovich Shevchenko, Sherzod Pardaboevich Abdullaev, Natalia Pavlovna Denisenko, Dmitry Vladimirovich Ivashchenko, Zhannet Alimovna Sozaeva, Anastasia Alekseevna Kachanova

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Abstract

Objective: The study of ABCB1 and CYP3A4/3A5 gene polymorphism genes is promising in terms of their influence on prothrombin time variability, the residual equilibrium concentration of direct oral anticoagulants (DOACs) in patients with atrial fibrillation and the development of new personalized approaches to anticoagulation therapy in these patients. The aim of the study is to evaluate the effect of ABCB1 (rs1045642) C>T; ABCB1 (rs4148738) C>T and CYP3A5 (rs776746) A>G, CYP3A4*22(rs35599367) C>T gene polymorphisms on prothrombin time level and residual equilibrium concentration of rivaroxaban in patients with atrial fibrillation.

Methods: In total 86 patients (42 men and 44 female), aged 67.24 ± 1.01 years with atrial fibrillation were enrolled in the study. HPLC mass spectrometry analysis was used to determine rivaroxaban residual equilibrium concentration. Prothrombin time data were obtained from patient records.

Results: The residual equilibrium concentration of rivaroxaban in patients with ABCB1 rs4148738 CT genotype is significantly higher than in patients with ABCB1 rs4148738 CC (P = 0.039). The analysis of the combination of genotypes did not find a statistically significant role of combinations of alleles of several polymorphic markers in increasing the risk of hemorrhagic complications when taking rivaroxaban.

Conclusion: Patients with ABCB1 rs4148738 CT genotype have a statistically significantly higher residual equilibrium concentration of rivaroxaban in blood than patients with ABCB1 rs4148738 CC genotype, which should be considered when assessing the risk of hemorrhagic complications and risk of drug-drug interactions. Further studies of the effect of rivaroxaban pharmacogenetics on the safety profile and efficacy of therapy are needed.

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ABCB1、CYP3A5、CYP3A4基因多态性对非瓣膜性房颤患者凝血酶原时间及利伐沙班剩余平衡浓度的影响

目的:ABCB1和CYP3A4/3A5基因多态性基因对房颤患者凝血酶原时间变异性、直接口服抗凝剂(DOACs)剩余平衡浓度的影响以及房颤患者抗凝治疗的个性化新方法的研究具有前景。本研究的目的是评价ABCB1 (rs1045642) C>T的作用;ABCB1 (rs4148738) C>T、CYP3A5 (rs776746) A>G、CYP3A4*22(rs35599367) C>T基因多态性对房颤患者凝血酶原时间水平和利伐沙班剩余平衡浓度的影响。方法:86例房颤患者(男42例，女44例)，年龄67.24±1.01岁。采用高效液相色谱质谱法测定利伐沙班残留平衡浓度。凝血酶原时间数据从患者记录中获得。结果:ABCB1 rs4148738 CT基因型患者的利伐沙班残留平衡浓度显著高于ABCB1 rs4148738 CC基因型患者(P = 0.039)。基因型组合分析未发现几种多态性标记的等位基因组合在服用利伐沙班时增加出血性并发症的风险中具有统计学意义。结论:ABCB1 rs4148738 CT基因型患者血液中利伐沙班残留平衡浓度高于ABCB1 rs4148738 CC基因型患者，在评估出血性并发症风险及药物-药物相互作用风险时应予以考虑。需要进一步研究利伐沙班药物遗传学对治疗安全性和有效性的影响。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.