华法林是治疗栓塞性疾病的一线药物，然而治疗窗窄、个体差异大一直是困扰其临床使用的关键问题。本课题组近年来以心脏瓣膜置换手术患者为对象，对与华法林抗凝作用和体内代谢相关的VKORC1、CYP2C9基因，以及在凝血通路中起重要作用的CYP4F2基因多态性与华法林维持剂量的相关性进行了广泛研究，获得了有临床指导意义的结果。近年来POR在药物代谢酶表达调控中的重要作用被逐渐认识，同时近几年来国际上的研究热点表药物蛋白质组学也日益受到关注，其中TTR被证实与华法林剂量个体差异有关联。本课题将在前期工作基础上，结合POR遗传多态性以及TTR表达水平，更全面地筛查与华法林维持剂量相关的影响因素，建立更完整的华法林维持剂量预测方程并通过临床应用进行验证。

Warfarin is an oral anticoagulant commonly prescribed for patients with venous thrombosis, pulmonary embolism, chronic atrial fibrillation and prosthetic heart valves. A narrow therapeutic range, wide inter-individual variation in drug response and the risk of bleeding all make warfarin a difficult drug to use clinically. In recent years, our team have studied the association between warfarin maintenance doses and related genes in warfarin pharmacokinetic, pharmacodynamic pathway, such as VKORC1, CYP2C9 and CYP4F2, and the result came out to be significant in clinical guides. These years, genetic polymorphisms of POR influencing P450 enzymes activity in drug metabolism is drawn great attention. Pharmacoproteomics also catches researchers' eyes, and TTR was found to be associated with warfarin doses variation. Based on our previous studies, this research aims to explore the relationship between POR polymorphism, TTR level and warfarin maintenance dose inter-individual variation, to set up more complete dose-predicted models for better use of warfarin.