药物代谢酶CYP2C9基因多态性

Genetic polymorphisms of CYP2C9

细胞色素氧化酶P450 2C9(CYP2C9)是人类肝脏中一类重要的药物代谢酶,负责约15%临床上常用药物(特别是一治疗安全范围较窄的药物)的代谢。CYP2C9基因具有高度多态性,研究表明该多态性与药物代谢和药物不良反应的产生关系密切。根据CYP2C9突变基因对CYP2C9酶活性的影响结果,一般可将CYP2C9的代谢表型划分为泛代谢型、中间代谢型和弱代谢型。近年来对该基因多态性及其与表型关系的研究再次成为遗传药理学研究的热点。本文从发生机制、代谢表型、药物代谢以及疾病的易感性等四个方面对CYP2C9基因多态性进行综述。

Human cytochrome P450 2C9 （CYP2C9） accounts for -20% of hepatic total cytochrome P450 content and metabolizes -15% clinical drugs, especially the drugs with a narrow therapeutic index. CYP2C9 is highly polymorphism. Many results have shown that the genetic polymorphisms of CYP2C9 have close relationship with drug metabolism and adverse drug reaction. According to CYP2C9 enzyme activity, CYP2C9 could be classified as extensive metabolizers, intermedia metabolizers and poor metabolizers. The relationship between genetic polymorphisms and phenotypes, have become the prevalent research topics in the area of pharmacogenetics. In this paper, we reviewed the genetic polymorphisms of CYP2C9 in four areas： the mechanism, metabolic phenotype, drug metabolism and disease susceptibility.