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

IF 0.8 Q3 MEDICINE, GENERAL & INTERNAL Caspian Journal of Internal Medicine Pub Date : 2024-01-01 DOI:10.22088/cjim.15.3.499

Ayan Abdrakhmanov, Elena Zholdybayeva, Aizhana Shaimerdinova, Gulmira Kulmambetova, Svetlana Abildinova, Rustam Albayev, Gulnara Tuyakova, Elena Rib, Zhanasyl Suleimen, Zhanar Abdrakhmanova, Makhabbat Bekbossynova

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Abstract

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.

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哈萨克斯坦人群中 ABCB1 和 CES1 基因变异对达比加群代谢的影响。

背景：编码酯酶系统（CES1）和P-糖蛋白（ABCB1）的基因的等位基因变异可改变达比加群的代谢和药代动力学。因此，它们是产生副作用，尤其是出血的决定性因素。我们分析了接受达比加群治疗的心房颤动患者中 ABCB1（rs1045642、rs4148738、rs2032582 和 rs1128503）和 CES1（rs8192935、rs71647871 和 rs2244613）多态性的基因型与表型关系：本研究共招募了 150 名患者。采用 TaqMan 技术进行 SNP 基因分型：结果：rs2244613 GG 基因型患者的血药浓度（55.27 ± 34.22 ng/ml）低于 TT 基因型患者（63.33 ± 52.25 ng/ml）（加性模型，P = 0.000）。rs8192935 AA 基因型个体的浓度（52.72 ± 30.45 ng/ml）低于 GG 基因型个体的浓度（79.78 ± 57 ng/ml）（加法模型，P = 0.001）。不同基因型的 ABCB1 SNPs（rs4148738 和 rs1045642）的 APTT 值有显著差异（分别为 P = 0.035 和 P = 0.024）：我们的研究表明，在哈萨克亚人群中，CES1 多态性 rs8192935 和 rs2244613 与达比加群的药效学和药代动力学有关。

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