title: Gene expression variability in human hepatic drug metabolizing enzymes and transporters.
abstract: 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.
authors: Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas, United States of America.
authors: Lun
authors: L
authors: Yang
authors: Elvin T
authors: ET
authors: Price
authors: Ching-Wei
authors: CW
authors: Chang
authors: Yan
authors: Y
authors: Li
authors: Ying
authors: Y
authors: Huang
authors: Li-Wu
authors: LW
authors: Guo
authors: Yongli
authors: Y
authors: Guo
authors: Jim
authors: J
authors: Kaput
authors: Leming
authors: L
authors: Shi
authors: Baitang
authors: B
authors: Ning
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism*; D053263:Gene Regulatory Networks; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D057285:Precision Medicine; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D059467:Transcriptome
chemical_list: D002352:Carrier Proteins; D004798:Enzymes; D004364:Pharmaceutical Preparations; D018160:Receptors, Cytoplasmic and Nuclear
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