Department of Pediatrics, Onco-Hematology Unit, Geneva University Hospitals, 1205 Geneva, Switzerland.
Curr Drug Metab. 2012 Oct;13(8):1196-204. doi: 10.2174/138920012802850146.
Cytochrome P450 2C19 (CYP2C19) is involved in the metabolism of several drugs that are currently in clinical use. The gene encoding CYP2C19 is polymorphic with the existence of different alleles resulting in altered enzyme activity. In addition, CYP2C19 activity is also dependent on its basal expression levels determined by the transcriptional regulation. Genetic variations located in the CYP2C19 promoter region may alter the interaction of promoter with transcription factors causing variable transcription. Genetic variants may also influence the induction, inhibition of CYP2C19 and may as well affect drug-drug interactions involving CYP2C19 substrates. The role of various transcription factors and genetic variants in the promoter region of CYP2C19 regulating its expression are discussed in this review. Furthermore, induction and inhibition of CYP2C19 by various drugs in clinically meaningful drug interactions are also discussed.
细胞色素 P450 2C19（CYP2C19）参与几种目前临床应用药物的代谢。编码 CYP2C19 的基因具有多态性，不同等位基因的存在导致酶活性改变。此外，CYP2C19 活性还依赖于其基础表达水平，这由转录调控决定。位于 CYP2C19 启动子区域的遗传变异可能改变启动子与转录因子的相互作用，从而导致转录的变化。遗传变异也可能影响 CYP2C19 的诱导和抑制，并且可能影响涉及 CYP2C19 底物的药物相互作用。本文综述了各种转录因子和遗传变异在 CYP2C19 启动子区域对其表达的调节作用。此外，还讨论了临床上有意义的药物相互作用中各种药物对 CYP2C19 的诱导和抑制作用。
