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Epigenetic Regulation of Cytochrome P450 Enzymes and Clinical Implication.

CYPs are a large and diverse group of drug-metabolizing enzymes, which govern the metabolism of the majority of xenobiotic substances as well as endogenous components. The high inter-subject variability of CYP bioactivity has been largely attributed to gene polymorphism until the rapid development in epigenetics in the last decade that revealed another aspect of regulatory mechanism of drug-related genes. Epigenetics is the study of changes in gene expression or cellular phenotype that are not caused by changes in the underlying DNA sequence. The modification of histone proteins, together with DNA methylation and miRNAs, is the most extensively studied epigenetic mechanism in mammals. Recently, it has been demonstrated that alterations in epigenetic regulation occur during multiple pathological processes, especially carcinogenesis. As CYPs play an important role in carcinogen and anti-cancer drug biotransformation, epigenetic changes in CYP genes would lead to interindividual differences in drug responses. In this review, we provide an up-to-date summary of epigenetic studies on human CYPs, and discuss how such information could be integrated with clinical application.