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细胞色素P450(CYPs)家族是体内重要的药物代谢酶,其功能主要是代谢临床药物及外源性物质。长期以来,CYP450酶的个体间功能活性差异往往被认为是由基因多态性所导致。然而随着研究的日益深入,人们发现基因序列的改变并不能完全解释CYP450酶的个体间活性差异。表观遗传学作为研究DNA序列未发生变化而基因表达发生可遗传变异的学科,可作为重要研究手段进一步解释CYP450酶的个体差异。该学科主要研究内容包括DNA甲基化、组蛋白翻译后修饰和RNA编辑等。本文就各主要CYP450酶的表观遗传学调控研究进行综述并讨论其在药物代谢和临床应用中的意义。
Cytochrome P450 (CYPs) family is an important drug metabolizing enzyme in the body, its main function is to metabolize clinical drugs and exogenous substances. For a long time, CYP450 enzyme activity differences between individuals is often considered to be caused by genetic polymorphisms. However, with the deepening of the research, it was found that the change of the gene sequence does not completely explain the difference in the individual activity of the CYP450 enzyme. Epigenetics, as a discipline that studies the inheritance of gene expression without any change in DNA sequence, can be used as an important research tool to further explain the individual differences in CYP450 enzymes. The main research topics include DNA methylation, histone post-translational modification and RNA editing. This review summarizes the studies on epigenetic regulation of major CYP450 enzymes and discusses their implications for drug metabolism and clinical applications.