Pharmacogenetic Variants of Warfarin Response Genes in the Kazakh Population: Implications for Personalized Anticoagulant Therapy

Genetic variants significantly influence the efficacy and safety of anticoagulants such as warfarin and acenocoumarol, making the study of key polymorphisms in the Kazakh population crucial for personalized medicine. This article aims to determine the frequency of actionable genetic variants in pharmacogenetic genes relevant to warfarin metabolism in Central Asian Kazakhs and to assess their significance for personalized anticoagulant therapy. The study included 1900 conditionally healthy respondents, evenly distributed by sex and age. The analysis focused on the allele frequencies of clinically relevant polymorphisms in the CYP2C9 (*2, *3, *5, *6), CYP2C19 (*1), VKORC1 (*1), CYP4F2 (*1), and GGCX (*1) genes. Notably, the *2 (rs1799853), *3 (rs1057910), *5 (rs28371686), and *6 (rs9332131) polymorphisms of CYP2C9, along with CYP2C19 (rs3814637), VKORC1 (rs9923231), CYP4F2 (rs2108622), and GGCX (rs11676382), were evaluated for their associations with warfarin metabolism and sensitivity. The CYP2C9 variants were present in 16.5% of the population, while the VKORC1 and CYP2C19 variants were found in 28.8% and 30%, respectively. The findings underscore the need for genotyping in this population to optimize warfarin dosing and minimize adverse drug reactions. Further studies will explore the clinical implications of these variants in the context of personalized anticoagulation therapy.