Variability in human hepatic MRP4 expression: influence of cholestasis and genotype
العنوان: | Variability in human hepatic MRP4 expression: influence of cholestasis and genotype |
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المؤلفون: | Matthias Schwab, Heyo K. Kroemer, Ulrich M. Zanger, B Anwald, Thomas Lang, Michel Eichelbaum, Elke Schaeffeler, Peter Fritz, Iouri Bachmakov, Gabriele Jedlitschky, Hartmut Glaeser, Martin F. Fromm, H Tegude, Kathrin Klein, Ulrike Gradhand, Reinhold Kerb |
المصدر: | The Pharmacogenomics Journal. 8:42-52 |
بيانات النشر: | Springer Science and Business Media LLC, 2007. |
سنة النشر: | 2007 |
مصطلحات موضوعية: | Adult, Male, Genotype, Protein Conformation, Biology, Polymorphism, Single Nucleotide, Exon, Cholestasis, Terminology as Topic, Genetic variation, Genetics, medicine, Humans, RNA, Messenger, Gene, Cellular localization, Pharmacology, Messenger RNA, Polymorphism, Genetic, Reverse Transcriptase Polymerase Chain Reaction, Intron, Genetic Variation, DNA, medicine.disease, Immunohistochemistry, Molecular biology, Introns, Gene Expression Regulation, Haplotypes, Liver, Microscopy, Fluorescence, Molecular Medicine, Female, Multidrug Resistance-Associated Proteins |
الوصف: | 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 |
تدمد: | 1473-1150 1470-269X |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::73869ea8954c1d1967d3b822f52454cbTest https://doi.org/10.1038/sj.tpj.6500451Test |
حقوق: | CLOSED |
رقم الانضمام: | edsair.doi.dedup.....73869ea8954c1d1967d3b822f52454cb |
قاعدة البيانات: | OpenAIRE |
تدمد: | 14731150 1470269X |
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