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

TL;DR

This study explores how genetic variations in two genes affect dabigatran metabolism in the Kazakh population, influencing drug concentration and bleeding risk.

Contribution

The study identifies specific CES1 and ABCB1 gene polymorphisms linked to dabigatran pharmacokinetics in a Kazakh population.

Findings

Patients with rs2244613 GG genotype had lower dabigatran concentrations compared to TT genotype carriers.

The rs8192935 AA genotype was associated with significantly lower dabigatran concentrations than the GG genotype.

ABCB1 SNPs rs4148738 and rs1045642 showed significant differences in APTT values among genotypes.

Abstract

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.

A total of 150 patients were recruited for this study. TaqMan technology was used for SNP genotyping.

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).

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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