RESUMEN
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.
Asunto(s)
Fibrilación Atrial , Citocromo P-450 CYP3A , Femenino , Humanos , Masculino , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/genética , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Genotipo , Polimorfismo Genético , Tiempo de Protrombina , Rivaroxabán/efectos adversos , AncianoRESUMEN
This study was aimed to investigate the prevalence of CYP2C9*2 (p.430C > T, rs1799853), CYP2C9*3 (p.1075A > C, rs1057910), CYP4F2*3 (p.1297G > A, rs2108622), CYP2C19*2 (p.681G > A, rs4244285), CYP2C19*3 (p.636G > A, rs4986893), CYP2C19*17 (p.1260C > A, rs12248560), ABCB1 (p.3435C > T, rs1045642), CYP2D6*4 (p.1846G > A, rs3892097), SLCO1B1*5 (p.521T > C, rs4149056) and CES1 (p.1168-33A > C, rs2244613) among Tatars and Balkars ethnic groups living in Russia to provide a basis for future clinical studies concerning on understanding of population-level differences in drug response. The study involved 341 apparently healthy, unrelated, and chronic medication-free volunteers of both sexes of ethnic groups of Tatars and Balkars living in Volga and Caucasus regions of Russia. Genotyping was performed using real-time polymerase chain reaction-based methods. The allelic prevalence of studied markers in ethnic groups were compared with Russians as a largest ethnic group in Russia. Statistically significant differences for the following gene polymorphisms were found between both ethnic groups in respect of different markers and with Russians. Our study shows differences in prevalence of the main relevant pharmacogenetic markers in Tatars and Balkars. These findings should be taken into consideration for personalization algorithms development and pharmacogenetics implementation in regions with ethnic minorities as Russia has.
Asunto(s)
Biomarcadores Farmacológicos/metabolismo , Etnicidad/genética , Población Blanca/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Adulto , Hidrolasas de Éster Carboxílico/genética , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C9/genética , Citocromo P-450 CYP2D6/genética , Familia 4 del Citocromo P450/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Transportador 1 de Anión Orgánico Específico del Hígado/genética , Masculino , Farmacogenética/métodos , Polimorfismo de Nucleótido Simple , Federación de Rusia/epidemiología , TranscriptomaRESUMEN
This study was aimed to investigate the prevalence of the CES1 gene (c.1168-33A > C, rs2244613) polymorphism among 12 different ethnic groups living in Russia to provide a basis for future clinical studies concerning genetic determinants of dabigatran safety. The study involved 1630 apparently healthy, unrelated, and chronic medication-free volunteers of both genders from 12 different ethnic groups in Russia: 136 Russians, 90 Avars, 50 Dargins, 46 Laks, 120 Kabardians, 112 Balkars, 244 Ossetians, 206 Mari, 204 Mordvinians, 238 Chuvashes, 114 Buryats and 70 Nanays. Genotyping was performed by using real-time polymerase chain reaction-based methods. The allelic prevalence of the ethnic groups was compared with Caucasus population participating in the RE-LY study. Statistically significant differences for the following gene polymorphism were found between all ethnic groups and RE-LY participants. Based on obtained results, it can be assumed that patients of all ethnic groups living in Russia taking dabigatran have a lower risk of bleeding.