Title:Epigenetic Regulation of Cytochrome P450 Enzymes and Clinical Implication
Volume: 16
Issue: 2
Author(s): Xiaojing Tang and Shuqing Chen
Affiliation:
Keywords:
Adverse drug reactions, cytochrome P450, DNA methylation, epigenetics, histone modification, microRNA, personalized medicine.
Abstract: 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.