Faculty Collaboration Database

ADME transcriptome in Hispanic versus White donor livers: evidence of a globally enhanced NR1I3 (CAR, constitutive androstane receptor) gene signature in Hispanics. Xenobiotica 2006;36(10-11):989-1012

Date

11/23/2006

Pubmed ID

17118917

DOI

10.1080/00498250600861769

Scopus ID

2-s2.0-33751573877 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

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.

Author List

Finkelstein D, Lamba V, Assem M, Rengelshausen J, Yasuda K, Strom S, Schuetz E

Author

Mahfoud Assem PharmD Associate Professor in the School of Pharmacy Administration department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Animals
Aryl Hydrocarbon Hydroxylases
Female
Gene Expression Profiling
Gene Expression Regulation
Humans
Liver
Male
Mice
Mice, Inbred C57BL
Middle Aged
Phenobarbital
RNA, Messenger
Receptors, Cytoplasmic and Nuclear
Receptors, Steroid
Reproducibility of Results
Tissue Donors
Transcription Factors
Transcription, Genetic
Xenobiotics