Genetic variants of ABCB1 and CES1 genes on dabigatran metabolism in the Kazakh population

Abdrakhmanov A. Zholdybayeva E. Shaimerdinova A. Kulmambetova G. Abildinova S. Albayev R. Tuyakova G. Rib E. Suleimen Z. Abdrakhmanova Z. Bekbossynova M.
2024 Babol University of Medical Sciences

Caspian Journal of Internal Medicine
2024 #15 Issue 3 499 - 508 pp.

Background: Allelic variants of genes encoding enzymes of the esterase system (CES1) and P-glycoprotein (ABCB1) can change the metabolism and pharmacokinetics of dabigatran. Therefore, they act as determining factors in the development of side effects, especially bleeding. We analyzed the genotype–phenotype relationship of ABCB1 (rs1045642, rs4148738, rs2032582, and rs1128503) and CES1 (rs8192935, rs71647871, and rs2244613) polymorphisms in patients with atrial fibrillation who had been treated with dabigatran. Methods: A total of 150 patients were recruited for this study. TaqMan technology was used for SNP genotyping. Results: Patients with the rs2244613 GG genotype had a lower concentration (55.27 ± 34.22 ng/ml) compared to those with the TT genotype (63.33 ± 52.25 ng/ml) (additive model, P = 0.000). Individuals with the rs8192935 AA genotype had a lower concentration (52.72 ± 30.45 ng/ml) compared to those with the GG genotype (79.78 ± 57 ng/ml) (additive model, P = 0.001). The APTT values among the different genotypes of the ABCB1 SNPs, rs4148738 and rs1045642, were significantly different (P = 0.035 and P = 0.024, respectively). Conclusion: Our research demonstrates that the CES1 polymorphisms, rs8192935 and rs2244613, are associated with the pharmacodynamics and pharmacokinetics of dabigatran in the Kazakh subpopulation.

ABCB1 , Atrial fibrillation , CES1 , Dabigatran , Genetic polymorphisms , Pharmacogenetics

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Department of Arrhythmology, National Research Cardiac Surgery Center, Turan 38, Astana, Kazakhstan
Hospital of the Medical Center of the Office of the President, Astana, E 495, Kazakhstan
National Center for Biotechnology, 13/5, Kurgalzhynskoye road, Astana, Kazakhstan
Medical University Astana, Beibitshilik St 49/A, Astana, Kazakhstan

Department of Arrhythmology
Hospital of the Medical Center of the Office of the President
National Center for Biotechnology
Medical University Astana

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