Variability in human hepatic MRP4 expression: influence of cholestasis and genotype.

Variability in human hepatic MRP4 expression: influence of cholestasis and genotype. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Variability in human hepatic MRP4 expression: influence of cholestasis and genotype. Abstract Text:

U Gradhand,T Lang,E Schaeffeler,H Glaeser,H Tegude,K Klein,P Fritz,G Jedlitschky,H K Kroemer,I Bachmakov,B Anwald,R Kerb,U M Zanger,M Eichelbaum,M Schwab,M F Fromm,

The multidrug resistance protein 4 (MRP4) is an efflux transporter involved in the transport of endogenous substrates and xenobiotics. We measured MRP4 mRNA and protein expression in human livers and found a 38- and 45-fold variability, respectively. We sequenced 2 kb of the 5'-flanking region, all exons and intron/exon boundaries of the MRP4 gene in 95 patients and identified 74 genetic variants including 10 non-synonymous variations, seven of them being located in highly conserved regions. None of the detected polymorphisms was significantly associated with changes in the MRP4 mRNA or protein expression. Immunofluorescence microscopy indicated that none of the non-synonymous variations affected the cellular localization of MRP4. However, in cholestatic patients the MRP4 mRNA and protein expression both were significantly upregulated compared to non-cholestatic livers (protein: 299+/-138 vs 100+/-60a.u., P<0.001). Taken together, human hepatic MRP4 expression is highly variable. Genetic variations were not sufficient to explain this variability. In contrast, cholestasis is one major determinant of human hepatic MRP4 expression.The Pharmacogenomics Journal (2008) 8, 42-52; doi:10.1038/sj.tpj.6500451; published online 3 April 2007.

Variability in human hepatic MRP4 expression: influence of cholestasis and genotype. Publishing Authors By Initials

U Gradhand,T Lang,E Schaeffeler,H Glaeser,H Tegude,K Klein,P Fritz,G Jedlitschky,HK Kroemer,I Bachmakov,B Anwald,R Kerb,UM Zanger,M Eichelbaum,M Schwab,MF Fromm,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Variability in human hepatic MRP4 expression: influence of cholestasis and genotype. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The pharmacogenomics journal

VOLUME: 8

Page Numbers: 42-52

Journal Abbreviation: Pharmacogenomics J.

ISSN: 1470-269X

DAY: 3

MONTH: 04

YEAR: 2007

Variability in human hepatic MRP4 expression: influence of cholestasis and genotype. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101083949

Variability in human hepatic MRP4 expression: influence of cholestasis and genotype. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Variability in human hepatic MRP4 expression: influence of cholestasis and genotype. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Variability in human hepatic MRP4 expression: influence of cholestasis and genotype.

AFFILIATION: 1Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Erlangen, Germany.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Pharmacogenomics J

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Variability in human hepatic MRP4 expression: influence of cholestasis and genotype Related Publications

• A new operation for the prevention and treatment of amputation neuromas.
• ATP-binding cassette transporters in human heart failure.
• AffyMiner: mining differentially expressed genes and biological knowledge in GeneChip microarray data.
• Analogy of the coordination chemistry of alkaline earth metal and lanthanide Ln(2+) ions: the isostructural zoo of mixed metal cages [IM(OtBu)4{Li(thf)}4(OH)] (M=Ca, Sr, Ba, Eu), [MM'6(OPh)8(thf)6] (M=Ca, Sr, Ba, Sm, Eu, M'=Li, Na), and their derivatives
• Animal models and intestinal drug transport.
• Banthine in the treatment of duodenal ulcer.
• Burn mortality. Experience at a regional burn unit. Literature review.
• Calmodulin-binding transcription activator (CAMTA) 3 mediates biotic defense responses in Arabidopsis.
• Chloralose induced alteration of visually evoked response from specific and non-specific regions of cat neocortex.
• Determinants of Steady-State Torasemide Pharmacokinetics : Impact of Pharmacogenetic Factors, Gender and Angiotensin II Receptor Blockers.
• Directing RNA interference specifically to differentiated muscle cells.
• Killing tumor cells: the effect of photodynamic therapy using mono-L-aspartyl chlorine and NS-398.
• Neuregulin-1 induces acetylcholine receptor transcription in the absence of GABPalpha phosphorylation.
• Not Available
• Origin of transverse fractures in the middle third of the face. A clinical and experimental study.
• Potassium-dependent cambial growth in poplar.
• Reverberation modeling with BiRASP-The bistatic range-dependent active system prediction model.
• Role of p-glycoprotein inhibition for drug interactions : evidence from in vitro and pharmacoepidemiological studies.
• Severe acute renal insufficiency with recovery.
• Shuttle expression plasmids for genetic studies in Streptococcus mutans.
• Static firing rates of premotor and primary motor cortical neurons associated with torque and joint position.
• The Oedipus myth.
• The association of ABCB1 polymorphisms and elevated serum digitoxin concentrations in geriatric patients.
• The precipitating effect of methanol on viruses.
• Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
• Unusual primary urethral calculus; case report.
• Variability in human hepatic MRP4 expression: influence of cholestasis and genotype.
• [Not Available.]
• [Not Available.]
• [The Revision of the Regulations Concerning Driving Licences (FeV) to Combat the Dangers of Sleep Apnoea and Insomnia in Road Traffic.]