title: Potential role of epigenetic mechanisms in the regulation of drug metabolism and transport.
abstract: This is a report of a symposium on the potential role of epigenetic mechanisms in the control of drug disposition sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 2013 meeting in Boston, MA, April 21, 2013. Epigenetics is a rapidly evolving area, and recent studies have revealed that expression of drug-metabolizing enzymes and transporters is regulated by epigenetic factors, including histone modification, DNA methylation, and noncoding RNAs. The symposium speakers provided an overview of genetic and epigenetic mechanisms underlying variable drug metabolism and drug response, as well as the implications for personalized medicine. Considerable insight into the epigenetic mechanisms in differential regulation of the dioxin-inducible drug and carcinogen-metabolizing enzymes CYP1A1 and 1B1 was provided. The role of noncoding microRNAs in the control of drug metabolism and disposition through targeting of cytochrome P450 (P450) enzymes and ATP-binding cassette membrane transporters was discussed. In addition, potential effects of xenobiotics on chromatin interactions and epigenomics, as well as the possible role of long noncoding RNAs in regulation of P450s during liver maturation were presented.
authors.affiliation: Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden (M.I.-S.); Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut (X.-B.Z., L.P.); Interdepartmental Molecular Toxicology Program and the Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California (O.H., S.B.); Department of Biochemistry and Molecular Medicine, University of California at Davis School of Medicine, Sacramento, California (A.-M.Y.); and Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (Y.O.).
authors.forename: Magnus
authors.initials: M
authors.lastname: Ingelman-Sundberg
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Zhong
authors.forename: Oliver
authors.initials: O
authors.lastname: Hankinson
authors.forename: Sudheer
authors.initials: S
authors.lastname: Beedanagari
authors.forename: Ai-Ming
authors.initials: AM
authors.lastname: Yu
authors.forename: Lai
authors.initials: L
authors.lastname: Peng
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Osawa
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001692:Biological Transport / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1
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