Mechanisms of genetic regulation in gene expression: examples from drug metabolizing enzymes and transporters

Abstract

Interindividual variability in the response to drug therapy is due, in part, to genetic mechanisms which influence the expression of genes involved with drug metabolism and transport. Genetic elements and processes such as DNA methylation, histone deacetylation, transcription factors, DNA sequence variants, and microRNAs (miRNAs) can impact at either the transcriptional or translational levels to modulate gene expression. Identification of such genetic regulators has greatly advanced in the last decade. Genome-wide analyses, using different types of approaches and methodologies, have uncovered many potential regulators of the expression of drug metabolizing enzymes and transporters. However, confirming the function of these putative regulators is necessary and requires further work in the laboratory, using techniques which are still evolving. It also still remains to be seen whether these findings have clinical implications for drug therapy but the realization of personalized medicine is a possible consequence of this research.