Received: 20.07.2026
Accepted: 13.10.2026
Published online: 30.10.2026
UDC: 616-08-039.73
DOI: 10.53511/pharmkaz.2026.5.1
Article type: Review article
WARFARIN PHARMACOGENETICS: MODERN INTERNATIONAL PERSONALIZED APPROACHES AND PROSPECTS FOR THEIR IMPLEMENTATION IN THE REPUBLIC OF KAZAKHSTAN
U.E. Imammyrzayev¹, I.K. Tulebayeva¹, B.A. Rakishev², K.E. Kazantayev², S.B. Pazilov³, A.K. Shulgabayev⁴
¹ Kazakhstan Medical University “KSPH”, Almaty, Republic of Kazakhstan
² A.N. Syzganov National Scientific Center of Surgery JSC, Almaty, Republic of Kazakhstan
³ City Polyclinic No. 10, Almaty, Republic of Kazakhstan
⁴ Sarkan Central District Hospital, Sarkan, Republic of Kazakhstan
Abstract
Warfarin remains an important anticoagulant for the prevention and treatment of thromboembolic complications, particularly in patients with mechanical heart valve prostheses. Substantial interindividual variability in warfarin dose requirements, influenced by genetic, clinical, and environmental factors, complicates the achievement of stable anticoagulation.
The aim of this review was to analyze international and Kazakhstani studies on pharmacogenetic factors influencing the response to warfarin, evaluate the evidence supporting genotype-guided dosing, and identify prospects for implementing personalized dosing algorithms in the Republic of Kazakhstan.
Materials and Methods
An analytical review was conducted of original molecular genetic studies, randomized controlled trials, systematic reviews, meta-analyses, and international guidelines. Particular attention was given to population genetic studies conducted in Kazakhstan and the findings of research project AP19677439.
Results
CYP2C9 and VKORC1 are the principal genetic determinants of individual warfarin dose requirements, while CYP4F2 has an additional influence. International pharmacogenetic algorithms improve the prediction of maintenance doses; however, randomized controlled trials have yielded inconsistent results regarding international normalized ratio (INR) control and clinical outcomes. Kazakhstan has established a scientific foundation for population pharmacogenetics and implemented a specialized research project investigating genetic factors associated with complications of warfarin therapy in cardiac surgery patients.
Conclusion
Independent clinical validation of a domestic clinical-pharmacogenetic model represents a promising direction for further research, with particular emphasis on anticoagulation stability, treatment safety, and pharmacoeconomic effectiveness.
Keywords: warfarin, pharmacogenetics, CYP2C9, VKORC1, CYP4F2, CYP2C19, GGCX, personalized medicine, Kazakhstan.
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