Potential role of epigenetic mechanisms in the regulation of drug metabolism and transport

Magnus Ingelman-Sundberg, Xiao Bo Zhong, Oliver Hankinson, Sudheer Beedanagari, Aiming Yu, Lai Peng, Yoichi Osawa

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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 and1B1 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.

Original languageEnglish (US)
Pages (from-to)1725-1731
Number of pages7
JournalDrug Metabolism and Disposition
Volume41
Issue number10
DOIs
StatePublished - Oct 2013

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Ingelman-Sundberg, M., Zhong, X. B., Hankinson, O., Beedanagari, S., Yu, A., Peng, L., & Osawa, Y. (2013). Potential role of epigenetic mechanisms in the regulation of drug metabolism and transport. Drug Metabolism and Disposition, 41(10), 1725-1731. https://doi.org/10.1124/dmd.113.053157