Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10-11
pubmed:dateCreated
2006-11-22
pubmed:abstractText
Previous studies have found that, compared with Whites, Hispanic donor livers had elevated expression of CYP2 enzymes, gene products regulated by the constitutive androstane receptor (CAR). The objectives of the current study were to determine (1) the CAR activation signature in human liver (2) whether other drug detoxification (absorption, distribution, metabolism and excretion (ADME)) genes were differentially expressed in Hispanic versus White livers, and (3) the extent of overlap in the CAR and Hispanic liver transcriptomes. The CAR transcriptome (ADME genes differentially expressed following phenobarbital versus vehicle treatment of human hepatocytes) and the Hispanic liver transcriptome (ADME genes differentially expressed in Hispanic versus White livers) were identified using Affymetrix oligonucleotide arrays. Quantitative real-time polymerase chain reaction (PCR) was used to verify candidate genes in a larger sample size. Comparison of the CAR and Hispanic liver ADME transcriptomes revealed a significant association between the gene changes. Sixty-four per cent of the ADME genes induced more than twofold by phenobarbital were also induced in Hispanics, and 14% of the ADME genes repressed more than twofold by phenobarbital were repressed in Hispanics. In conclusion, compared with Whites, Hispanic donor livers have increased expression of many genes that are transcriptionally regulated by CAR. This result has practical implications to the drug treatment of Hispanic patients.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0049-8254
pubmed:author
pubmed:issnType
Print
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
989-1012
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17118917-Adolescent, pubmed-meshheading:17118917-Adult, pubmed-meshheading:17118917-Aged, pubmed-meshheading:17118917-Animals, pubmed-meshheading:17118917-Aryl Hydrocarbon Hydroxylases, pubmed-meshheading:17118917-European Continental Ancestry Group, pubmed-meshheading:17118917-Female, pubmed-meshheading:17118917-Gene Expression Profiling, pubmed-meshheading:17118917-Gene Expression Regulation, pubmed-meshheading:17118917-Hispanic Americans, pubmed-meshheading:17118917-Humans, pubmed-meshheading:17118917-Liver, pubmed-meshheading:17118917-Male, pubmed-meshheading:17118917-Mice, pubmed-meshheading:17118917-Mice, Inbred C57BL, pubmed-meshheading:17118917-Middle Aged, pubmed-meshheading:17118917-Phenobarbital, pubmed-meshheading:17118917-RNA, Messenger, pubmed-meshheading:17118917-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:17118917-Receptors, Steroid, pubmed-meshheading:17118917-Reproducibility of Results, pubmed-meshheading:17118917-Tissue Donors, pubmed-meshheading:17118917-Transcription, Genetic, pubmed-meshheading:17118917-Transcription Factors, pubmed-meshheading:17118917-Xenobiotics
pubmed:articleTitle
ADME transcriptome in Hispanic versus White donor livers: evidence of a globally enhanced NR1I3 (CAR, constitutive androstane receptor) gene signature in Hispanics.
pubmed:affiliation
The Hartwell Center, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural