Shendre Aditi, Dillon Chrisly, Limdi Nita A
Department of Epidemiology, Richard M Fairbanks School of Public Health, Indiana University Purdue University Indianapolis, IN 46202, USA.
Department of Neurology, School of Medicine, University of Alabama at Birmingham, AL 35294, USA.
Pharmacogenomics. 2018 Nov;19(17):1357-1371. doi: 10.2217/pgs-2018-0146. Epub 2018 Oct 22.
Despite the introduction of direct acting oral anticoagulants, warfarin remains the most commonly prescribed oral anticoagulant. However, warfarin therapy is plagued by the large inter- and intrapatient variability. The variability in dosing fueled research to identify clinical and genetic predictors and develop more accurate dosing algorithms. Observational studies have demonstrated the significant impact of single nucleotide polymorphisms in CYP2C9 and VKORC1 on warfarin dose in patients of European ancestry and African-Americans. This evidence supported the design and conduct of clinical trials to assess whether genotype-guided dosing results in improved anticoagulation control and outcomes. The trial results have shown discordance by race, with pharmacogenetic algorithms improving dose and anticoagulation control among European ancestry patients compared with African-American patients. Herein, we review the evidence from observational and interventional studies, highlight the need for inclusion of minority race groups and propose the need to develop race specific dosing algorithms.
尽管直接口服抗凝剂已被引入，但华法林仍然是最常用的口服抗凝剂。然而，华法林治疗受到患者间和患者内较大变异性的困扰。剂量的变异性推动了对临床和基因预测因素的研究，并促使人们开发更准确的给药算法。观察性研究表明，细胞色素P450 2C9（CYP2C9）和维生素K环氧化物还原酶复合体亚单位1（VKORC1）中的单核苷酸多态性对欧洲血统患者和非裔美国人的华法林剂量有重大影响。这一证据支持了评估基因分型指导给药是否能改善抗凝控制及预后的临床试验的设计与开展。试验结果显示，不同种族之间存在差异，与非裔美国患者相比，药物遗传学算法在欧洲血统患者中改善了剂量和抗凝控制。在此，我们回顾了观察性和干预性研究的证据，强调纳入少数种族群体的必要性，并提出开发种族特异性给药算法的必要性。
