Makohusová Miroslava, Mrázová Viera, Bednárová Adriána, Milatová Eva, Sokol Jozef, Pleško Marek, Bátorová Angelika
Department of Chemistry, Faculty of Natural Sciences, University of SS Cyril and Methodius, Trnava, Slovak Republic.
Department of Pediatric Hematology and Oncology, Comenius University - Faculty of Medicine and National Institute of Children's Diseases, Bratislava, Slovak Republic.
Iran J Pharm Res. 2019 Spring;18(2):1010-1019. doi: 10.22037/ijpr.2019.1100653.
A high prevalence of genetic polymorphisms increases sensitivity to warfarin therapy. In this study, we investigated 47 patients with effective long-term therapy by warfarin well-controlled by monitoring of International Normalised Ratio (INR). All patients were tested for gene polymorphisms VKORC1, CYP2C9C2, and CYP2C9C3, which were used for a dose calculation employing a program www.WarfarinDosing.org. The main goal was to investigate whether the warfarin doses determined by INR are in accordance with the doses calculated according to the pharmacogenetic algorithm. For this purpose, several chemometric tools, namely principal component analysis, cluster analysis, correlation analysis, correspondence analysis, Passing-Bablock regression, Bland-Altman method, descriptive statistics, and ANOVA were used. We also analysed the relationship between the dose of warfarin determined by INR and several constitutional and genetic factors. Statistically significant association between clinically optimized warfarin dose and indication for the treatment, age, and warfarin sensitivity determined by VKORC1, CYP2C9 gene polymorphisms were confirmed. Finally, we confirmed a good concordance between the INR determined warfarin doses and pharmacogenetic approach.
基因多态性的高流行率增加了对华法林治疗的敏感性。在本研究中，我们调查了47例通过监测国际标准化比值（INR）实现华法林长期有效控制的患者。对所有患者进行了VKORC1、CYP2C9C2和CYP2C9C3基因多态性检测，并使用www.WarfarinDosing.org程序进行剂量计算。主要目的是研究根据INR确定的华法林剂量是否与根据药物遗传学算法计算的剂量一致。为此，使用了几种化学计量学工具，即主成分分析、聚类分析、相关性分析、对应分析、Passing-Bablock回归、Bland-Altman方法、描述性统计和方差分析。我们还分析了根据INR确定的华法林剂量与几个体质和遗传因素之间的关系。临床优化的华法林剂量与治疗指征、年龄以及由VKORC1、CYP2C9基因多态性确定的华法林敏感性之间存在统计学显著关联。最后，我们证实了根据INR确定的华法林剂量与药物遗传学方法之间具有良好的一致性。
