MicroRNA-Dependent Gene Regulation of the Human Cytochrome P450

Abstract The cytochrome P450 (CYP) superfamily catalyzes the majority of the phase I drug-metabolizing reactions in humans. Variations in the expression and activity of drug-metabolizing enzymes and transporters between different individuals have a major impact on drug efficacy and drug safety. Individual differences in genetic and epigenetic regulation of CYP expression can affect drug metabolism and drug response. MicroRNAs (miRNAs) are small noncoding RNA molecules that repress gene expression posttranscriptionally. miRNAs participate in regulating CYP gene expression, which influences CYP-dependent drug metabolism. This chapter describes direct and indirect epigenetic molecular mechanisms for the regulation of CYP expression by miRNAs along with research strategies applied in the elucidation of these systems. Clinical implications are also presented for drug-drug interactions and adverse drug interactions influenced by miRNA-CYP regulatory interactions.