Tomek Aleš, Růžičková Tereza, Kaplan Vojtěch, Lacinová Zuzana, Kumstýřová Simona, Šrámek Martin, Olšerová Anna, Janský Petr, Kolářová Tereza, Neumann Jiří, Schwabová Jaroslava Paulasová, Maťoška Václav
Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, V Uvalu 84, Prague, Czech Republic.
Department of Clinical Biochemistry, Haematology and Immunology, Laboratory of Molecular Genetics, Hospital Na Homolce, Prague, Czech Republic.
Drug Metab Pers Ther. 2020 Dec 22. doi: 10.1515/dmdi-2020-0171.
Warfarin use is limited by a low therapeutic index and significant interindividual variability of the daily dose. The most important factor predicting daily warfarin dose is individual genotype, polymorphisms of genes (warfarin metabolism) and (sensitivity for warfarin). Algorithms using clinical and genetic variables could predict the daily dose before the initiation of therapy. The aim of this study was to develop and validate an algorithm for the prediction of warfarin daily dose in Czech patients.
Detailed clinical data of patients with known and stable warfarin daily dose were collected. All patients were genotyped for polymorphisms in genes and .
Included patients were divided into derivation (n=175) and validation (n=223) cohorts. The final algorithm includes the following variables: Age, height, weight, treatment with amiodarone and presence of variant alleles of genes and . The adjusted coefficient of determination is 72.4% in the derivation and 62.3% in the validation cohort (p<0.001).
Our validated algorithm for warfarin daily dose prediction in our Czech cohort had higher precision than other currently published algorithms. Pharmacogenetics of warfarin has the potential in the clinical practice in specialized centers.
华法林的使用受到低治疗指数和每日剂量显著个体间差异的限制。预测华法林每日剂量的最重要因素是个体基因型、基因（华法林代谢）和（对华法林的敏感性）的多态性。使用临床和遗传变量的算法可以在治疗开始前预测每日剂量。本研究的目的是开发并验证一种用于预测捷克患者华法林每日剂量的算法。
收集已知且稳定的华法林每日剂量患者的详细临床数据。所有患者均进行基因和基因多态性的基因分型。
纳入的患者分为推导队列（n = 175）和验证队列（n = 223）。最终算法包括以下变量：年龄、身高、体重、胺碘酮治疗以及基因和基因变异等位基因的存在情况。推导队列中的调整决定系数为72.4%，验证队列中为62.3%（p < 0.001）。
我们在捷克队列中验证的华法林每日剂量预测算法比目前其他已发表的算法具有更高的精度。华法林的药物遗传学在专科中心的临床实践中具有潜力。
