基因多态性预测华法林维持剂量的研究进展

Research Progress in the Effects of Gene Polymorphisms on Warfarin Maintenance Doses

华法林是最常应用的口服抗凝药物之一。许多研究已证实华法林维持剂量的个体差异与细胞色素P450 2C9(CYP2C9)和维生素K环氧化物还原酶复合物1(VKORC1)的基因型密切相关。纳入基因信息和临床数据的剂量计算公式可预测华法林的维持剂量。但目前已开展的临床试验结果不一,对其实用性提出了质疑。虽然现有证据并不支持采用基因型分析指导华法林维持剂量,但在有条件的机构针对特定族群开展基因型检测也不失为一种合理的选择。目前正在进行的试验有望提供更多数据,下一步研究需要在剂量公式中纳入适用于少数人群的变量。所有这些工作将进一步完善临床应用基因型检测指导华法林剂量这一新型的治疗模式。

Warfarin is one of the most frequently prescribed oral anticoagulant. Many researches have shown that the cytochrome P450 2C9 （CYP2Cg） and vitamin K epoxide reductase complex 1 （VKORC1） genotypes have been strongly associated with warfarin maintenance doses. Warfarin maintenance doses can be accurately predicted by use of dosing algorithms including genetic and clinical information. Although several clinical trials demonstrated mixed results, calling into question the utility of this approach. The present data do not support genetic testing to guide warfarin maintenance doses, but in the setting where genotype data are available, use of this approach is reasonable. Ongoing trials are expected to provide more data, and more work is needed to define dosing algorithms that include appropriate variables in minority populations. All these work will further improve the clinical application of genotype-guided warfarin maintenance doses.