Open AccessGene Expression Variability in Human Hepatic Drug Metabolizing Enzymes and Transporters
Author(s) -
Lun Yang,
Elvin Price,
ChingWei Chang,
Yan Li,
Ying Huang,
Lei Guo,
Yongli Guo,
Jim Kaput,
Leming Shi,
Baitang Ning
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0060368
Subject(s) - gene , gene expression , biology , gene expression profiling , microarray , microarray analysis techniques , dna microarray , genetics , computational biology
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.