Epigenetic regulation of genes encoding drug-metabolizing enzymes and transporters; DNA methylation and other mechanisms

Takeshi Hirota, Hiroshi Takane, Shun Higuchi, Ichiro Ieiri

研究成果: Contribution to journalReview article査読

23 被引用数 (Scopus)

抄録

Drug metabolizing enzymes and transporters are increasingly recognized as key determinants of the inter-individual variability in pharmacokinetic (PK) and pharmacodynamic (PD) outcomes of clinically important drugs. To date, most studies investigating this variability have focused on polymorphisms (e.g. SNPs) in the genes encoding metabolic enzymes and transporters; however, it has recently been reported that the expression of some of these genes is under the control of epigenetic mechanisms. The most common epigenetic mechanism of mammalian genome regulation is DNA methylation, which does not change the genetic code but affects gene expression. Owing to its maintenance of the genomic sequence, DNA methylation is expected to offer an explanation for the controversial phenotypes of certain genetic polymorphisms. It has been recognized that DNA methylation plays a role in the transcrptional regulation of some PK/PD genes. In this review, we describe the impact of various epigenetic mechanism, especially DNA methylation, on the expression (or activity) of drug metabolizing enzymes and transporter genes.

本文言語英語
ページ(範囲)34-38
ページ数5
ジャーナルCurrent Drug Metabolism
9
1
DOI
出版ステータス出版済み - 1 1 2008

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Clinical Biochemistry

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