The Distribution of the Genotypes of ABCB1 and CES1 Polymorphisms in Kazakhstani Patients with Atrial Fibrillation Treated with DOAC
Abdrakhmanov A. Akilzhanova A. Shaimerdinova A. Zhalbinova M. Tuyakova G. Abildinova S. Albayev R. Ainabekova B. Chinybayeva A. Suleimen Z. Bekbossynova M.
June 2023Multidisciplinary Digital Publishing Institute (MDPI)
Genes
2023#14Issue 6
Nowadays, direct oral anticoagulants (DOACs) are the first-line anticoagulant strategy in patients with non-valvular atrial fibrillation (NVAF). We aimed to identify the influence of polymorphisms of the genes encoding P-glycoprotein (ABCB1) and carboxylesterase 1 (CES1) on the variability of plasma concentrations of DOACs in Kazakhstani patients with NVAF. We analyzed polymorphisms rs4148738, rs1045642, rs2032582 and rs1128503 in ABCB1 and rs8192935, rs2244613 and rs71647871 CES1 genes and measured the plasma concentrations of dabigatran/apixaban and biochemical parameters in 150 Kazakhstani NVAF patients. Polymorphism rs8192935 in the CES1 gene (p = 0.04), BMI (p = 0.01) and APTT level (p = 0.01) were statistically significant independent factors of trough plasma concentration of dabigatran. In contrast, polymorphisms rs4148738, rs1045642, rs2032582 and rs1128503 in ABCB1 and rs8192935, rs2244613 and rs71647871 CES1 genes did not show significant influence on plasma concentrations of dabigatran/apixaban drugs (p > 0.05). Patients with GG genotype (138.8 ± 100.1 ng/mL) had higher peak plasma concentration of dabigatran than with AA genotype (100.9 ± 59.6 ng/mL) and AG genotype (98.7 ± 72.3 ng/mL) (Kruskal–Wallis test, p = 0.25). Thus, CES1 rs8192935 is significantly associated with plasma concentrations of dabigatran in Kazakhstani NVAF patients (p < 0.05). The level of the plasma concentration shows that biotransformation of the dabigatran processed faster in individual carriers of GG genotype rs8192935 in the CES1 gene than with AA genotype.
ABCB1 , apixaban , CES1 , dabigatran , NVAF , pharmacogenetics
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National Research Cardiac Surgery Center, Astana, 010000, Kazakhstan
Medical Centre Hospital of President’s Affairs Administration of the Republic of Kazakhstan, Astana, 010000, Kazakhstan
Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, 010000, Kazakhstan
Department of Internal Medicine, Medical University Astana, Astana, 010000, Kazakhstan
Corporate Fund “University Medical Center”, Nazarbayev University, Astana, 010000, Kazakhstan
National Research Cardiac Surgery Center
Medical Centre Hospital of President’s Affairs Administration of the Republic of Kazakhstan
Center for Life Sciences
Department of Internal Medicine
Corporate Fund “University Medical Center”
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