Epigenetic regulation of ADME-related genes: focus on drug metabolism and transport.
Epigenetic regulation of gene expression refers to heritable factors that are functionally relevant genomic modifications but that do not involve changes in DNA sequence. Examples of such modifications include DNA methylation, histone modifications, noncoding RNAs, and chromatin architecture. Epigenetic modifications are crucial for packaging and interpreting the genome, and they have fundamental functions in regulating gene expression and activity under the influence of physiologic and environmental factors. Recently, epigenetics has become one of the fastest-growing areas of science and has now become a central issue in biologic studies of development and disease pathogenesis. The interest in epigenetics is also true for studies of drug metabolism and transport. In this issue of Drug Metabolism and Disposition, a series of articles is presented to demonstrate the role of epigenetic factors in regulating the expression of genes involved in drug absorption, distribution, metabolism, and excretion in organ development, tissue-specific gene expression, sexual dimorphism, and in the adaptive response to xenobiotic exposure, both therapeutic and toxic. The articles also demonstrate that, in addition to genetic polymorphisms, epigenetics may also contribute to wide interindividual variations in drug metabolism and transport. Identification of functionally relevant epigenetic biomarkers in human specimens has the potential to improve prediction of drug responses based on patient's epigenetic profiles.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (X.B.Z.); and Division of Clinical Pharmacology and Therapeutic Innovation, Department of Pediatrics, Children's Mercy Hospitals and Clinics and University of Missouri-Kansas City, Kansas City, Missouri (J.S.L.).
Xiao-bo
XB
Zhong
J Steven
JS
Leeder
D000042:Absorption / Q000235:genetics*; D001692:Biological Transport / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D057890:Epigenomics / Q000379:methods; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D014018:Tissue Distribution / Q000235:genetics*
D004364:Pharmaceutical Preparations