Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients
Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients
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DOI：
10.1038/jhg.2011.4
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发表时间：
2011-04-01
影响因子：
3.5
通讯作者：
Kang, Jin-Hyoung
中科院分区：
文献类型：
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作者：
Choi, Jung Ran;Kim, Jeong-Oh;Kang, Jin-Hyoung
华法林是预防血栓栓塞性疾病的常用处方抗凝药物。我们调查了四个基因的遗传变异和临床因素对华法林剂量需求的贡献，并提供了一个基于韩国患者遗传和临床变量的华法林剂量算法。我们招募了564名接受稳定抗凝治疗的韩国患者。分析VKORC 1、CYP 2C 9、CYP 4F 2和GGCX的单核苷酸多态性（SNP）。使用多元回归分析，我们开发了一个模型来预测华法林的需求。VKORC 1、CYP 2C 9、CYP 4F 2和GGCX的SNPs与华法林剂量显著相关。3730 AA基因型患者接受的华法林剂量显著高于3730 GG基因型患者（P=0.0001）。对于CYP 2C 9，观察到野生型基因型患者的维持剂量最高，与变异等位基因携带者相比（P < 0.0001）。包括年龄、性别、体表面积（BSA）、国际标准化比值（INR）和4种基因多态性的多元回归模型解释了华法林剂量总变异的35%（R-2=0.3499; P < 0.0001）。本研究表明，年龄，性别，BSA，INR和VKORC 1，CYP 2C 9和CYP 4F 2多态性影响华法林的剂量要求在韩国人。将这些知识转化为华法林处方的临床指南可能有助于提高韩国患者华法林治疗的疗效和安全性。Journal of Human Genetics（2011）56，290-295; doi：10.1038/jhg.2011.4; 2011年2月17日在线发表
Warfarin is a commonly prescribed anticoagulant drug for the prevention of thromboembolic disorders. We investigated the contribution of genetic variations of four genes and clinical factors to warfarin dose requirement and provided a warfarin-dosing algorithm based on genetic and clinical variables in Korean patients. We recruited 564 Korean patients on stable anticoagulation. Single nucleotide polymorphisms (SNPs) for the VKORC1, CYP2C9, CYP4F2 and GGCX were analyzed. Using multiple regression analysis, we developed a model to predict the warfarin requirement. The SNPs of VKORC1, CYP2C9, CYP4F2 and GGCX showed significant correlation with warfarin dose. Patients with the 3730AA genotype received significantly higher doses of warfarin than those with the 3730GG (P=0.0001). For CYP2C9, the highest maintenance dose was observed in the patients with wild-type genotype compared with the variant allele carriers (P < 0.0001). The multiple regression model including age, gender, body surface area (BSA), international normalized ratio (INR) and four genetic polymorphisms accounted for 35% of total variations in warfarin dose (R-2=0.3499; P < 0.0001). This study shows that age, gender, BSA, INR and VKORC1, CYP2C9 and CYP4F2 polymorphism affect warfarin dose requirements in Koreans. Translation of this knowledge into clinical guidelines for warfarin prescription may contribute to improve the efficacy and safety of warfarin treatment for Korean patients. Journal of Human Genetics (2011) 56, 290-295; doi:10.1038/jhg.2011.4; published online 17 February 2011