Gene expression variability in human hepatic drug metabolizing enzymes and transporters

PLoS One. 2013 Apr 23;8(4):e60368. doi: 10.1371/journal.pone.0060368. Print 2013.


Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs) in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Enzymes / genetics*
  • Enzymes / metabolism*
  • Gene Regulatory Networks
  • Humans
  • Liver / enzymology
  • Liver / metabolism*
  • Pharmaceutical Preparations / metabolism*
  • Precision Medicine
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Transcriptome*


  • Carrier Proteins
  • Enzymes
  • Pharmaceutical Preparations
  • Receptors, Cytoplasmic and Nuclear

Grants and funding

LY, YL and LG were supported by appointments to the Postgraduate Research Program at the National Center for Toxicological Research administered by Oak Ridge Institute for Science Education through an interagency agreement between the United States Department of Energy and the Federal Drug Administration. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.