12 research outputs found

    Gene Expression Variability in Human Hepatic Drug Metabolizing Enzymes and Transporters

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    <div><p></p><p>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.</p> </div

    Drug-gene interaction network.

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    <p>The figure indicates the relationship among the ten most influential DMETs and the top 100 prescribed medications. A line between a gene and a drug suggest that the DMET is involved in the metabolism or transporting of the drug. A drug is labeled as a circle and a gene is labeled.</p

    Regulation pathways for DMET expression by GeneGo analysis.

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    <p>The figure indicates the relationship among the ten most influential DMETs and drugs (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060368#pone-0060368-t002" target="_blank">Table 2</a>), and the most common nuclear receptors (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060368#pone-0060368-t003" target="_blank">Table 3</a>). The Panel A indicats the CAR/RXR mediated pathways in the regulation of DMET gene expression, and the Panel B indicates the PXR/RXR mediated pathways in the regulation of DMET gene expression. Panel C lists the legends to visualize the GeneGo pathway maps.</p

    The visualization of the coexpression network for DMET genes.

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    <p>The graph highlights that genes in a liver coexpression network fall into 10 distinct modules, where genes within a module are more highly interconnected with each other than with genes outside the module.</p

    Concordance in genotypes between replicates of the same subject within a genotyping platform and within a genotyping experiment.

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    <p>The averaged concordance values (the bars) and the corresponding standard deviations (the error bars) between replicates of a subject (coded by color as: blue for A, red for B, cyan for C, Magenta for D, Green for E, and Orange for F) genotyped in a genotyping experiment (indicated at x-axis) are plotted. The subject codes and the experiment ID for genotyping experiments are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044483#pone-0044483-t001" target="_blank">Table 1</a>.</p
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