CYP2C9 and VKORC1 variants and warfarin response in Kazakh patients following cardiac surgery.

Q2 Pharmacology, Toxicology and Pharmaceutics

Drug metabolism and personalized therapy Pub Date : 2026-10-07 DOI:10.1515/dmpt-2026-0030

Gulnara Svyatova, Galina Berezina, Alexandra Murtazaliyeva, Yergali Miyerbekov, Ualikhan Imammurzaev

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引用次数: 0

Abstract

Objectives: To evaluate the association between CYP2C9 and VKORC1 polymorphisms and warfarin therapy outcomes in Kazakh patients following cardiac surgery, with a focus on dose requirements, INR stabilisation and bleeding complications.

Methods: A retrospective cohort study was conducted among 186 Kazakh patients (108 men and 78 women; mean age 59.2 ± 8.4 years) who underwent cardiac surgery and received warfarin therapy for at least 3 months. Clinical data and pharmacogenetic results were analysed from electronic medical records. The studied variants included CYP2C9 (2, 3) and VKORC1 (-1639G>A). Associations between genotype groups, warfarin dose requirements, INR control and adverse events were assessed.

Results: Patients with the CYP2C9 3/3 genotype required the lowest mean daily warfarin dose (1.9 ± 0.4 mg), whereas CYP2C9 1/1 carriers required the highest dose (4.8 ± 0.6 mg). Genotype-guided dosing was associated with faster INR stabilisation compared with conventional dosing (12.3 ± 3.9 vs. 20.5 ± 5.7 days) and a lower incidence of clinically significant bleeding events (6.2 vs. 14.8 %).

Conclusions: The findings demonstrate that *CYP2C9* and *VKORC1* variants contribute to variability in warfarin response among Kazakh patients after cardiac surgery. Incorporating pharmacogenetic information into clinical decision-making may improve dose individualisation, anticoagulation control and treatment safety. Further prospective multicentre studies are required to confirm these findings.

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哈萨克心脏手术后患者CYP2C9和VKORC1变异和华法林反应

目的：评估哈萨克心脏手术后患者CYP2C9和VKORC1多态性与华法林治疗结果之间的关系，重点关注剂量要求、INR稳定和出血并发症。方法：回顾性队列研究186例哈萨克患者（男性108例，女性78例，平均年龄59.2±8.4岁），均行心脏手术并接受华法林治疗至少3个月。从电子病历中分析临床资料和药物遗传学结果。研究的变异包括CYP2C9（2,3）和VKORC1 （-1639G>A）。评估基因型组、华法林剂量要求、INR控制和不良事件之间的关系。结果：CYP2C9 3/3基因型患者平均每日华法林剂量最低（1.9±0.4 mg），而CYP2C9 1/1基因型携带者每日华法林剂量最高（4.8±0.6 mg）。与常规给药相比，基因型引导给药与更快的INR稳定相关（12.3±3.9天vs. 20.5±5.7天），并且具有临床意义的出血事件发生率更低（6.2 vs. 14.8 %）。结论：研究结果表明，*CYP2C9*和*VKORC1*变异导致哈萨克族心脏手术后华法林反应的变异性。将药物遗传信息纳入临床决策可以改善剂量个体化、抗凝控制和治疗安全性。需要进一步的前瞻性多中心研究来证实这些发现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug metabolism and personalized therapy Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)

CiteScore

2.30

自引率

0.00%

发文量

期刊介绍： Drug Metabolism and Personalized Therapy (DMPT) is a peer-reviewed journal, and is abstracted/indexed in relevant major Abstracting Services. It provides up-to-date research articles, reviews and opinion papers in the wide field of drug metabolism research, covering established, new and potential drugs, environmentally toxic chemicals, the mechanisms by which drugs may interact with each other and with biological systems, and the pharmacological and toxicological consequences of these interactions and drug metabolism and excretion. Topics: drug metabolizing enzymes, pharmacogenetics and pharmacogenomics, biochemical pharmacology, molecular pathology, clinical pharmacology, pharmacokinetics and drug-drug interactions, immunopharmacology, neuropsychopharmacology.