ADME transcriptome in Hispanic versus White donor livers: evidence of a globally enhanced NR1I3 (CAR, constitutive androstane receptor) gene signature in Hispanics.

ADME transcriptome in Hispanic versus White donor livers: evidence of a globally enhanced NR1I3 (CAR, constitutive androstane receptor) gene signature in Hispanics. Research Abstract Details 

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ADME transcriptome in Hispanic versus White donor livers: evidence of a globally enhanced NR1I3 (CAR, constitutive androstane receptor) gene signature in Hispanics. Abstract Text:

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

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.

ADME transcriptome in Hispanic versus White donor livers: evidence of a globally enhanced NR1I3 (CAR, constitutive androstane receptor) gene signature in Hispanics. Publishing Authors By Initials

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

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ADME transcriptome in Hispanic versus White donor livers: evidence of a globally enhanced NR1I3 (CAR, constitutive androstane receptor) gene signature in Hispanics. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Xenobiotica; the fate of foreign compounds in biol

VOLUME: 36

Page Numbers: 989-1012

Journal Abbreviation: Xenobiotica

ISSN: 0049-8254

DAY: 3

MONTH: 12

YEAR: 2007

ADME transcriptome in Hispanic versus White donor livers: evidence of a globally enhanced NR1I3 (CAR, constitutive androstane receptor) gene signature in Hispanics. Information

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LANGUAGE: eng

NlmUniqueID: 1306665

ADME transcriptome in Hispanic versus White donor livers: evidence of a globally enhanced NR1I3 (CAR, constitutive androstane receptor) gene signature in Hispanics. Keywords Mesh Terms:

KEYWORDS: Xenobiotics

MESH TERMS: metabolism

Chemical & Substance for Abstract: ADME transcriptome in Hispanic versus White donor livers: evidence of a globally enhanced NR1I3 (CAR, constitutive androstane receptor) gene signature in Hispanics. Information

Substance Name: Aryl Hydrocarbon Hydroxylases

Registry Number: EC 1.14.14.1

Grant and Affiliation Information for ADME transcriptome in Hispanic versus White donor livers: evidence of a globally enhanced NR1I3 (CAR, constitutive androstane receptor) gene signature in Hispanics.

AFFILIATION: The Hartwell Center, St Jude Children's Research Hospital, Memphis, TN 38105, USA.

Country: England

AGENCY: United States NIGMS

GRANT: U01GM61393

ACRONYM: GM

MEDLINETA: Xenobiotica

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