The drug metabolism is a biochemical process on modification of pharmaceutical substances through specialized enzymatic systems. Changes in the expression of drug-metabolizing enzyme genes can affect drug metabolism. Recently, epigenetic regulation of drug-metabolizing enzyme genes has emerged as an important mechanism. Epigenetic regulation refers to heritable factors of genomic modifications that do not involve changes in DNA sequence. Examples of such modifications include DNA methylation, histone modifications, and non-coding RNAs. This review examines the widespread effect of epigenetic regulations on genes involved in drug metabolism, and also suggests a network perspective of epigenetic regulation. The epigenetic mechanisms have important clinical implications and may provide insights into effective drug development and improve safety of drug therapy.
Keywords: CAR, constitutive androstane receptor; DNA methylation; DNMTs, DNA methyltransferases; Drug metabolism; Epigenetics; H3K27me3, histone 3 lysine 27 trimethylation; H3K36me3, histone 3 lysine 36 trimethylation; H3K4me1, histone 3 lysine 4 monomethylation; H3K4me2, histone 3 lysine 4 dimethylation; H3K4me3, histone 3 lysine 4 trimethylation; H3K9me2, histone 3 lysine 9 dimethylation; H3K9me3, histone 3 lysine 9 trimethylation; HATs, histone acetyltransferases; HDAC, histone deacetylases; Histone modification; Non-coding RNA; P450s, cytochrome P450s; SULTs, sulfotransferases; TSS, transcription start sites; Transporter; UGTs, UDP-glucuronosyltransferases; UTR, untranslated region; lncRNAs, long non-coding RNAs; miRNAs, microRNAs; ncRNAs, non-coding RNAs.