The role of pharmacogenetics in personalizing anticoagulant therapy: data from the Astrakhan region

The metabolic characteristics of anticoagulants largely depend on the patient’s genetic profile, determining the variability of pharmacological response to drugs and the risk of adverse reactions. Among the key genes encoding enzymes responsible for anticoagulant metabolism are CES1, CYP2C9, and VKORC1. They significantly influence the pharmacokinetics and pharmacodynamics of both indirect and direct oral anticoagulants, which dictates the effectiveness and safety of anticoagulant therapy. In clinical practice, the implementation of pharmacogenetic testing before prescribing anticoagulants will significantly reduce the risk of complications and improve therapeutic efficacy.

The aim. To assess the frequency of clinically significant polymorphisms of the CYP2C9 (rs1799853), VKORC1 (rs9912121), and CES1 (rs2244613) genes in patients residing in the Astrakhan region.

Materials and Methods. The study sample consisted of 90 patients residing in the Astrakhan region who received inpatient treatment for confirmed coronavirus infection COVID-19 and were receiving anticoagulants. Venous blood collected in EDTA tubes was examined: diagnostic kits “CYP2C9 gene Arg144Cys (rs1799853)” (NPF Sintol LLC, Russia), “VKORC1 gene G1639A (G3673A) (rs9923231)” (NPF Sintol LLC, Russia), and “CES1 gene C(-33)A (rs2244613) GenTest” (NMT LLC, Russia). After DNA isolation and amplification, blood samples were genotyped by PCR. The study was conducted with an assessment of Hardy–Weinberg equilibrium (p > 0.05).

Results. The results showed that the frequency of VKORC1 gene polymorphisms occurred in 60 (66.7%) patients (95% CI: [56.96–76.44]; p > 0.05), CES1 gene in 55 (61.1%) (95% CI: [51.03–71.17]; p > 0.05), and CYP2C9 gene in 24 (26.7%) (95% CI: [17.56–35.84], p > 0.05).

Conclusion. The obtained results revealed a high frequency of distribution of polymorphic variants of genes associated with altered pharmacological response to anticoagulant therapy in patients residing in the Astrakhan region. This highlights the potential for implementing pharmacogenetic testing in the regional healthcare clinical practice for a personalized approach, optimized dosing, and reduced risks of adverse outcomes.

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