Ulrich M Zanger

Summary

Affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology
Country: Germany

Publications

  1. ncbi request reprint Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation
    Ulrich M Zanger
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstr 112, 70376, Stuttgart, Germany
    Anal Bioanal Chem 392:1093-108. 2008
  2. pmc Paraoxonase (PON1 and PON3) Polymorphisms: Impact on Liver Expression and Atorvastatin-Lactone Hydrolysis
    Stephan Riedmaier
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, University of Tuebingen Stuttgart, Germany
    Front Pharmacol 2:41. 2011
  3. pmc Genomics of ADME gene expression: mapping expression quantitative trait loci relevant for absorption, distribution, metabolism and excretion of drugs in human liver
    A Schroder
    Center for Bioinformatics Tuebingen ZBIT, University of Tuebingen, Tuebingen, Germany
    Pharmacogenomics J 13:12-20. 2013
  4. pmc MIRNA-DISTILLER: A Stand-Alone Application to Compile microRNA Data from Databases
    Jessica K Rieger
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, University of Tuebingen Stuttgart, Germany
    Front Genet 2:39. 2011
  5. pmc Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance
    Ulrich M Zanger
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology Stuttgart, Germany The University of Tuebingen Tuebingen, Germany
    Front Genet 4:24. 2013
  6. doi request reprint Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation
    Ulrich M Zanger
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstr 112 D, 70376 Stuttgart, Germany
    Pharmacol Ther 138:103-41. 2013
  7. pmc A systems biology approach to dynamic modeling and inter-subject variability of statin pharmacokinetics in human hepatocytes
    Joachim Bucher
    Institute of Biochemical Engineering, Allmandring, and Center Systems Biology, Nobelstraße, University of Stuttgart, Germany
    BMC Syst Biol 5:66. 2011
  8. ncbi request reprint Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry
    Ulrich M Zanger
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, 70376, Stuttgart, Germany
    Naunyn Schmiedebergs Arch Pharmacol 369:23-37. 2004
  9. doi request reprint Aberrant splicing caused by single nucleotide polymorphism c.516G>T [Q172H], a marker of CYP2B6*6, is responsible for decreased expression and activity of CYP2B6 in liver
    Marco H Hofmann
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany and University of Tübingen, Auerbachstrasse 112, 70376 Stuttgart, Germany
    J Pharmacol Exp Ther 325:284-92. 2008
  10. ncbi request reprint Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance
    Ulrich M Zanger
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D 70376 Stuttgart, Germany
    Pharmacogenomics 8:743-59. 2007

Detail Information

Publications75

  1. ncbi request reprint Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation
    Ulrich M Zanger
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstr 112, 70376, Stuttgart, Germany
    Anal Bioanal Chem 392:1093-108. 2008
    ..In this review, we provide an up-to-date summary of the functional polymorphisms and aspects of the functional genomics of the major human drug-metabolizing cytochrome P450s, as well as their clinical significance...
  2. pmc Paraoxonase (PON1 and PON3) Polymorphisms: Impact on Liver Expression and Atorvastatin-Lactone Hydrolysis
    Stephan Riedmaier
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, University of Tuebingen Stuttgart, Germany
    Front Pharmacol 2:41. 2011
    ..In conclusion, PON-locus polymorphisms affect PON1 expression whereas non-genetic factors have an effect on PON1 and PON3 expression. This may influence response to therapy or adverse events in statin treatment...
  3. pmc Genomics of ADME gene expression: mapping expression quantitative trait loci relevant for absorption, distribution, metabolism and excretion of drugs in human liver
    A Schroder
    Center for Bioinformatics Tuebingen ZBIT, University of Tuebingen, Tuebingen, Germany
    Pharmacogenomics J 13:12-20. 2013
    ..This study extends our knowledge about the genetics of inter-individual variability of gene expression with particular emphasis on pharmacogenomics...
  4. pmc MIRNA-DISTILLER: A Stand-Alone Application to Compile microRNA Data from Databases
    Jessica K Rieger
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, University of Tuebingen Stuttgart, Germany
    Front Genet 2:39. 2011
    ..The software, a data example file and a tutorial are freely available at http://www.ikp-stuttgart.de/content/language1/html/10415.asp...
  5. pmc Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance
    Ulrich M Zanger
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology Stuttgart, Germany The University of Tuebingen Tuebingen, Germany
    Front Genet 4:24. 2013
    ....
  6. doi request reprint Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation
    Ulrich M Zanger
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstr 112 D, 70376 Stuttgart, Germany
    Pharmacol Ther 138:103-41. 2013
    ..Here we review the recent progress on drug metabolism activity profiles, interindividual variability and regulation of expression, and the functional and clinical impact of genetic variation in drug metabolizing P450s...
  7. pmc A systems biology approach to dynamic modeling and inter-subject variability of statin pharmacokinetics in human hepatocytes
    Joachim Bucher
    Institute of Biochemical Engineering, Allmandring, and Center Systems Biology, Nobelstraße, University of Stuttgart, Germany
    BMC Syst Biol 5:66. 2011
    ..Predicting individual drug biotransformation capacity requires quantitative and detailed models...
  8. ncbi request reprint Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry
    Ulrich M Zanger
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, 70376, Stuttgart, Germany
    Naunyn Schmiedebergs Arch Pharmacol 369:23-37. 2004
    ..Whether and how brain functions may be influenced by polymorphic expression are interesting questions for the future...
  9. doi request reprint Aberrant splicing caused by single nucleotide polymorphism c.516G>T [Q172H], a marker of CYP2B6*6, is responsible for decreased expression and activity of CYP2B6 in liver
    Marco H Hofmann
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany and University of Tübingen, Auerbachstrasse 112, 70376 Stuttgart, Germany
    J Pharmacol Exp Ther 325:284-92. 2008
    ..These results establish the single nucleotide polymorphism 516G>Tasthe causal sequence variation for severely decreased expression and function associated with CYP2B6*6...
  10. ncbi request reprint Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance
    Ulrich M Zanger
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D 70376 Stuttgart, Germany
    Pharmacogenomics 8:743-59. 2007
    ..In this review, we summarize general biomolecular and pharmacological features and present a detailed up-to-date description of genetic polymorphisms, including a discussion of recent clinical applications of CYP2B6 pharmacogenetics...
  11. ncbi request reprint A natural variant of the heme-binding signature (R441C) resulting in complete loss of function of CYP2D6
    Kathrin Klein
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart and University of Tuebingen, Auerbachstr 112, D 70376 Stuttgart, Germany
    Drug Metab Dispos 35:1247-50. 2007
    ..e., the invariant cysteine 2). This suggests that heme binding in mammalian P450s depends not only on the integrity of the heme-binding signature but also on other family- and subfamily-specific sequence determinants...
  12. ncbi request reprint PPARA: a novel genetic determinant of CYP3A4 in vitro and in vivo
    Kathrin Klein
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Clin Pharmacol Ther 91:1044-52. 2012
    ..These findings have implications for variability in response to drug substrates of CYP3A4...
  13. doi request reprint Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver
    Anne T Nies
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Hepatology 50:1227-40. 2009
    ..0001), and four variants in OCT3 (rs2292334, rs2048327, rs1810126, rs3088442) were associated with reduced OCT3 mRNA levels (P = 0.03)...
  14. ncbi request reprint Role of genetic and nongenetic factors for fluorouracil treatment-related severe toxicity: a prospective clinical trial by the German 5-FU Toxicity Study Group
    Matthias Schwab
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, University of Stuttgart, Stuttgart, Germany
    J Clin Oncol 26:2131-8. 2008
    ....
  15. ncbi request reprint Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes
    Werner Schroth
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D 70376 Stuttgart, Germany
    J Clin Oncol 25:5187-93. 2007
    ..We investigated the predictive value of genetic variants of CYP2D6, CYP2C19, and three other cytochrome P450 enzymes for tamoxifen treatment outcome...
  16. pmc The influence of CYP2B6, CYP2C9 and CYP2D6 genotypes on the formation of the potent antioestrogen Z-4-hydroxy-tamoxifen in human liver
    Janet K Coller
    Dr Margarete Fischer Bosch Institut für Klinische Pharmakologie, Auerbachstrasse 112, D 70376 Stuttgart, Germany
    Br J Clin Pharmacol 54:157-67. 2002
    ....
  17. ncbi request reprint The induction of cytochrome P450 3A5 (CYP3A5) in the human liver and intestine is mediated by the xenobiotic sensors pregnane X receptor (PXR) and constitutively activated receptor (CAR)
    Oliver Burk
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D 70376 Stuttgart, Germany
    J Biol Chem 279:38379-85. 2004
    ..In this manner, induction of CYP3A5 may contribute to the overall importance of this P450 in drug metabolism and drug interactions...
  18. ncbi request reprint A novel intronic mutation, 2988G>A, with high predictivity for impaired function of cytochrome P450 2D6 in white subjects
    Sebastian Raimundo
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Clin Pharmacol Ther 76:128-38. 2004
    ..Their identification is clinically relevant but remains unsatisfactory because of incomplete characterization of the major allele involved, termed CYP2D6*41 (-1584C, R296C, S486T)...
  19. doi request reprint Pharmacogenomics of human liver cytochrome P450 oxidoreductase: multifactorial analysis and impact on microsomal drug oxidation
    Ana M Gomes
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Auerbachstrasse 112, 70376 Stuttgart, Germany
    Pharmacogenomics 10:579-99. 2009
    ..We investigated genetic and nongenetic POR variability and its impact on drug-oxidation activities in human liver microsomes...
  20. ncbi request reprint Direct transcriptional regulation of human hepatic cytochrome P450 3A4 (CYP3A4) by peroxisome proliferator-activated receptor alpha (PPARα)
    Maria Thomas
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstr 112, 70376 Stuttgart, Germany
    Mol Pharmacol 83:709-18. 2013
    ..Furthermore, our data suggest that nutritional status can influence drug biotransformation capacity via endogenous phospholipid signaling...
  21. ncbi request reprint Association between the C3435T MDR1 gene polymorphism and susceptibility for ulcerative colitis
    Matthias Schwab
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, 70376 Stuttgart, Germany
    Gastroenterology 124:26-33. 2003
    ..Because the MDR1 single nucleotide polymorphism C3435T is associated with lower intestinal P-glycoprotein expression, we tested whether this polymorphism predisposes to development of ulcerative colitis...
  22. ncbi request reprint CYP2D6 genotyping strategy based on gene copy number determination by TaqMan real-time PCR
    Elke Schaeffeler
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Hum Mutat 22:476-85. 2003
    ..The predictability of the new strategy was systematically evaluated. The semiautomatic TaqMan assay allows high sample throughput and will be useful for pharmacogenetic studies and in the clinical setting...
  23. ncbi request reprint Three novel thiopurine S-methyltransferase allelic variants (TPMT*20, *21, *22) - association with decreased enzyme function
    Elke Schaeffeler
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Hum Mutat 27:976. 2006
    ..In Caucasians the occurrence of these genetic variants appears to be extremely rare since none of these alleles were identified in a randomly selected control population of 1048 individuals...
  24. ncbi request reprint MALDI-TOF mass spectrometry for multiplex genotyping of CYP2B6 single-nucleotide polymorphisms
    Julia K Blievernicht
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Clin Chem 53:24-33. 2007
    ..Several nonsynonymous and promoter single-nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with altered hepatic expression and function, which affect drug plasma concentrations...
  25. pmc Large interindividual variability in the in vitro formation of tamoxifen metabolites related to the development of genotoxicity
    Janet K Coller
    Dr Margarete Fischer Bosch Institut für Klinische Pharmakologie, Auerbachstr 112, D 70376 Stuttgart, Germany
    Br J Clin Pharmacol 57:105-11. 2004
    ..To characterize the interindividual variability and the individual CYP involved in the formation of alpha-hydroxy-, N-desmethyl- and N-didesmethyl-tamoxifen from tamoxifen...
  26. ncbi request reprint Detection of single nucleotide polymorphisms in CYP2B6 gene
    Ulrich M Zanger
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, D 70 376 Stuttgart, Germany
    Methods Enzymol 357:45-53. 2002
  27. ncbi request reprint Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants
    Elke Schaeffeler
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Pharmacogenetics 14:407-17. 2004
    ..Thus, the results of this study provide a solid basis to predict TPMT phenotype in a Northern European Caucasian population by molecular diagnostics...
  28. ncbi request reprint Sex is a major determinant of CYP3A4 expression in human liver
    Renzo Wolbold
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D 70376 Stuttgart, Germany
    Hepatology 38:978-88. 2003
    ..John's wort was found. In conclusion, sex, in addition to PXR and drug exposure, is a major factor for CYP3A4 expression in humans, thus explaining many of the previous observations of sex-dependent drug clearance...
  29. ncbi request reprint Genetic variability of CYP2B6 in populations of African and Asian origin: allele frequencies, novel functional variants, and possible implications for anti-HIV therapy with efavirenz
    Kathrin Klein
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Pharmacogenet Genomics 15:861-73. 2005
    ..17 (T26S, D28G, R29T) appeared to be functionally normal. These data extend the CYP2B6 knowledge base and should be particularly relevant for anti-HIV-therapy with efavirenz...
  30. doi request reprint Inferring statin-induced gene regulatory relationships in primary human hepatocytes
    Adrian Schröder
    Center for Bioinformatics Tuebingen, University of Tuebingen, Tuebingen, Germany
    Bioinformatics 27:2473-7. 2011
    ..However, statins elicit pleitropic responses including beneficial as well as adverse effects in the liver or other organs. Today, the regulatory mechanisms that cause these pleiotropic effects are not sufficiently understood...
  31. doi request reprint A predominate role of CYP1A2 for the metabolism of nabumetone to the active metabolite, 6-methoxy-2-naphthylacetic acid, in human liver microsomes
    Miia Turpeinen
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D 70376 Stuttgart, Germany
    Drug Metab Dispos 37:1017-24. 2009
    ..Taken together, these studies indicate that the formation of the active metabolite of nabumetone, 6-MNA, is predominantly catalyzed by CYP1A2 in HLMs with only minor contribution of other P450s...
  32. ncbi request reprint Genetic polymorphisms of glutathione S-transferase A1, the major glutathione S-transferase in human liver: consequences for enzyme expression and busulfan conjugation
    Monika Bredschneider
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Clin Pharmacol Ther 71:479-87. 2002
    ....
  33. ncbi request reprint A natural CYP2B6 TATA box polymorphism (-82T--> C) leading to enhanced transcription and relocation of the transcriptional start site
    Jörg Zukunft
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Mol Pharmacol 67:1772-82. 2005
    ..Furthermore, a detailed interspecies comparison of CYP2B promoters and transcriptional start sites provided novel insights into evolutionary relationships...
  34. ncbi request reprint Mutational analysis of the human dihydropyrimidine dehydrogenase gene by denaturing high-performance liquid chromatography
    Joachim Fischer
    Margarete Fischer Bosch Institute of Clinical Pharmacology, D 70376 Stuttgart, Germany
    Genet Test 7:97-105. 2003
    ..Sequence analysis confirmed all base changes detected. This method will be useful in identifying patients at risk for toxicity prior to 5-FU treatment, as well as in the analysis of individual patients with thymine-uraciluria...
  35. doi request reprint Highly multiplexed genotyping of thiopurine s-methyltransferase variants using MALD-TOF mass spectrometry: reliable genotyping in different ethnic groups
    Elke Schaeffeler
    Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany, and University of Tuebingen, Tuebingen, Germany
    Clin Chem 54:1637-47. 2008
    ..To avoid severe hematotoxicity in patients, determination of the TPMT (thiopurine S-methyltransferase) genotype before commencing thiopurine therapy has become accepted...
  36. doi request reprint Expression variability of absorption, distribution, metabolism, excretion-related microRNAs in human liver: influence of nongenetic factors and association with gene expression
    Jessica K Rieger
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany and University of Tuebingen, Tuebingen, Germany
    Drug Metab Dispos 41:1752-62. 2013
    ..g., miR-130b, miR-185, miR-34a), and CYP2E1 (miR-10a, let-7g, miR-200c). These data should be useful to further elucidate regulatory functions of miRNAs in liver pathophysiology and regulation of ADME gene expression. ..
  37. doi request reprint ABCC11/MRP8 polymorphisms affect 5-fluorouracil-induced severe toxicity and hepatic expression
    Tarek Magdy
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D 70376 Stuttgart, Germany
    Pharmacogenomics 14:1433-48. 2013
    ..Because 5-fluorodeoxyuridine monophosphate (5-FdUMP), an anabolic active metabolite of 5-fluorouracil (5-FU), is a substrate of MRP8 (encoded by ABCC11), we investigated whether ABCC11 polymorphisms play a role in severe toxicity of 5-FU...
  38. ncbi request reprint Potent mechanism-based inhibition of human CYP2B6 by clopidogrel and ticlopidine
    Tanja Richter
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    J Pharmacol Exp Ther 308:189-97. 2004
    ..These results suggest the possibility of drug interactions between thienopyridine derivates and drug substrates of CYP2B6 and CYP2C19...
  39. ncbi request reprint Molecular mechanisms of polymorphic CYP3A7 expression in adult human liver and intestine
    Oliver Burk
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D 70376 Stuttgart, Germany
    J Biol Chem 277:24280-8. 2002
    ..We conclude that the presence of the ER6 motif of CYP3A4 mediates the high expression of CYP3A7 in subjects carrying CYP3A7*1C...
  40. ncbi request reprint Molecular mechanism of basal CYP3A4 regulation by hepatocyte nuclear factor 4alpha: evidence for direct regulation in the intestine
    Heike Tegude
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D 70376 Stuttgart, Germany
    Drug Metab Dispos 35:946-54. 2007
    ..In summary, we here have elucidated a molecular mechanism of direct regulation of CYP3A4 by HNF4alpha, which is probably specific for the intestine...
  41. ncbi request reprint Azathioprine therapy and adverse drug reactions in patients with inflammatory bowel disease: impact of thiopurine S-methyltransferase polymorphism
    Matthias Schwab
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Pharmacogenetics 12:429-36. 2002
    ....
  42. ncbi request reprint Inhibition of human CYP2B6 by N,N',N''-triethylenethiophosphoramide is irreversible and mechanism-based
    Tanja Richter
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstr 112, 70376 Stuttgart, Germany
    Biochem Pharmacol 69:517-24. 2005
    ..These findings contribute to better understanding of drug interactions with thioTEPA...
  43. ncbi request reprint Influence of omeprazole on multidrug resistance protein 3 expression in human liver
    Monika Hitzl
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    J Pharmacol Exp Ther 304:524-30. 2003
    ..05), in HepG2 cells treated with omeprazole. Finally, MRP3 was induced in HepG2 cells by beta-naphthoflavone. In summary, treatment with omeprazole and beta-naphthoflavone is a determinant of variable human hepatic MRP3 expression...
  44. pmc DNA methylation is associated with downregulation of the organic cation transporter OCT1 (SLC22A1) in human hepatocellular carcinoma
    Elke Schaeffeler
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, 70376 Stuttgart, Germany
    Genome Med 3:82. 2011
    ..Therefore, we investigated the role of DNA methylation in the transcriptional regulation of the family members SLC22A1/OCT1, SLC22A2/OCT2 and SLC22A3/OCT3 in HCC...
  45. ncbi request reprint Discriminative quantification of cytochrome P4502D6 and 2D7/8 pseudogene expression by TaqMan real-time reverse transcriptase polymerase chain reaction
    Karin Endrizzi
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, 70376 Stuttgart, Germany
    Anal Biochem 300:121-31. 2002
    ..46, P < 0.0001) but did not depend on CYP2D6 genotype. These data demonstrate genotype-dependent mRNA expression for CYP2D6 and they emphasize the necessity of differentiating between the functional CYP2D6 and the CYP2D pseudogenes...
  46. ncbi request reprint Profiling induction of cytochrome p450 enzyme activity by statins using a new liquid chromatography-tandem mass spectrometry cocktail assay in human hepatocytes
    Diana M Feidt
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, Stuttgart, Germany
    Drug Metab Dispos 38:1589-97. 2010
    ..Our cocktail assay should be helpful for economical use of human hepatocytes in the assessment of P450 induction by drugs and drug candidates...
  47. ncbi request reprint Sensitive method for the quantification of urinary pyrimidine metabolites in healthy adults by gas chromatography-tandem mass spectrometry
    Ute Hofmann
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D 70376 Stuttgart, Germany
    J Chromatogr B Analyt Technol Biomed Life Sci 791:371-80. 2003
    ..The method was used for investigating the stability of urine samples and the influence of urine collection at different times...
  48. ncbi request reprint Expression polymorphism of the blood-brain barrier component P-glycoprotein (MDR1) in relation to Parkinson's disease
    Taku Furuno
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstr 112, 70376 Stuttgart, Germany
    Pharmacogenetics 12:529-34. 2002
    ..In conclusion, MDR1 and other drug transporters represent plausible candidates as Parkinson's disease risk genes. Larger studies are required to confirm this role in the etiology of Parkinson's disease...
  49. ncbi request reprint RNA-interference approach to study functions of NADPH : cytochrome P450 oxidoreductase in human hepatocytes
    Diana M Feidt
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Auerbachstrasse 112, DE 70376 Stuttgart
    Chem Biodivers 6:2084-91. 2009
    ..This will allow systematic studies of various consequences of POR variability in human cells...
  50. doi request reprint Novel CYP2B6 enzyme variants in a Rwandese population: functional characterization and assessment of in silico prediction tools
    Robert Radloff
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Hum Mutat 34:725-34. 2013
    ..Because low-activity alleles of CYP2B6 are associated with impaired EFV metabolism and adverse drug response, these results are of potential utility for personalized treatment strategies in HIV/AIDS therapy...
  51. pmc Pathway-Targeted Pharmacogenomics of CYP1A2 in Human Liver
    Kathrin Klein
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, University of Tuebingen Stuttgart, Germany
    Front Pharmacol 1:129. 2010
    ..In conclusion, we identified novel trans-associations between regulatory genes and hepatic CYP1A2 function and expression, but additional genetic factors must be assumed to explain the full extent of CYP1A2 heritability...
  52. doi request reprint No activation of human pregnane X receptor by hyperforin-related phloroglucinols
    Benjamin A Kandel
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany B A K, U M Z University of Tübingen, Tubingen, Germany B A K, U M Z Collaborations in Chemistry, Fuquay Varina, North Carolina S E Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland S E Department of Pharmacology, Rutgers University Robert Wood Johnson Medical School, Piscataway, New Jersey S E Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina S E Molecular and Clinical Pharmacy, Friedrich Alexander University, Erlangen Nuremberg, Germany K L Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich, Germany W E T and Institute of Pharmacology and Toxicology, Interfaculty Centre for Pharmacogenomics and Drug Research, University of Tubingen, Tubingen, Germany C H
    J Pharmacol Exp Ther 348:393-400. 2014
    ..These results show that TRPC6-activating phloroglucinols do not activate PXR and should therefore be promising new candidates for further drug development. ..
  53. pmc Pharmacogenomics of Cytochrome P450 3A4: Recent Progress Toward the "Missing Heritability" Problem
    Kathrin Klein
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart Stuttgart, Germany University of Tübingen Tübingen, Germany
    Front Genet 4:12. 2013
    ....
  54. ncbi request reprint Sex-dependent genetic markers of CYP3A4 expression and activity in human liver microsomes
    Markus Schirmer
    Georg August University, Department of Clinical Pharmacology, Gottingen, Germany
    Pharmacogenomics 8:443-53. 2007
    ..To find genetic markers of the individual cytochrome P450 (CYP)3A expression...
  55. ncbi request reprint Association of genetic polymorphism in ABCC2 with hepatic multidrug resistance-associated protein 2 expression and pravastatin pharmacokinetics
    Mikko Niemi
    Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
    Pharmacogenet Genomics 16:801-8. 2006
    ..Our aim was to investigate possible effects of sequence variations in ABCC2, encoding the multidrug resistance-associated protein 2 (MRP2), on the pharmacokinetics of the MRP2 substrate pravastatin...
  56. ncbi request reprint Limited contribution of CYP3A5 to the hepatic 6beta-hydroxylation of testosterone
    Landry K Kamdem
    Department of Clinical Pharmacology, Georg August University Gottingen, Robert Koch Strasse 40, 37099, Germany
    Naunyn Schmiedebergs Arch Pharmacol 370:71-7. 2004
    ..However, the contribution of CYP3A5 to 6beta-hydroxylation of testosterone in Caucasian livers is limited, due to the much lower expression levels of CYP3A5...
  57. ncbi request reprint Multiple novel nonsynonymous CYP2B6 gene polymorphisms in Caucasians: demonstration of phenotypic null alleles
    Thomas Lang
    EPIDAUROS Biotechnologie AG, AM Neuland, Bernried, Germany
    J Pharmacol Exp Ther 311:34-43. 2004
    ..6% in a Caucasian study population. These data provide further insight into the genetic variability of CYP2B6 and demonstrate the existence of phenotypic null alleles in this gene...
  58. ncbi request reprint Genetic polymorphisms in the multidrug resistance-associated protein 3 (ABCC3, MRP3) gene and relationship to its mRNA and protein expression in human liver
    Thomas Lang
    Epidauros Biotechnology, Pharmacogenetics Laboratory, Am Neuland 1, 82347 Bernried, Germany
    Pharmacogenetics 14:155-64. 2004
    ..To determine the genetic variability of multidrug resistance protein 3 (MRP3)...
  59. ncbi request reprint Bupropion and 4-OH-bupropion pharmacokinetics in relation to genetic polymorphisms in CYP2B6
    Julia Kirchheiner
    Institute of Clinical Pharmacology, University Medical Center Charite, Humboldt University, Berlin, Germany
    Pharmacogenetics 13:619-26. 2003
    ..The role of this allele should also be studied in other CYP2B6 substrates, including cyclophosphamide, halothane, mianserin, promethazine and propofol...
  60. ncbi request reprint V79 Chinese hamster cells genetically engineered for polymorphic cytochrome P450 2D6 and their predictive value for humans
    Niels Krebsfaenger
    GenPharmTox BioTech AG, D Planegg Martinsried
    ALTEX 20:143-54. 2003
    ..Based on these results, CYP-mediated metabolism of tamoxifen was investigated...
  61. ncbi request reprint A naturally occurring mutation in the SLC21A6 gene causing impaired membrane localization of the hepatocyte uptake transporter
    Christoph Michalski
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, D 69120 Heidelberg, Germany
    J Biol Chem 277:43058-63. 2002
    ..Importantly, most of the mutant protein SLC21A6-L193R was retained intracellularly, and this single amino acid exchange abolished transport function...
  62. ncbi request reprint Non-synonymous polymorphisms in the human SLCO1B1 gene: an in vitro analysis of SNP c.1929A>C
    Annick Seithel
    Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich Alexander University Erlangen Nuremberg, Fahrstrasse 17, Erlangen, Germany
    Mol Genet Genomics 279:149-57. 2008
    ..1929A>C had no effect on the hepatic OATP1B1 protein expression and on the transport properties. Therefore, it is unlikely that c.1929A>C contributes to interindividual variability in drug disposition...
  63. ncbi request reprint ABCB1 genotype of the donor but not of the recipient is a major risk factor for cyclosporine-related nephrotoxicity after renal transplantation
    Ingeborg A Hauser
    Department of Nephrology, Medical Clinic IV, University Hospital Johann Wolfgang Goethe University, Theodor Stern Kai 7, D 60596 Frankfurt am Main, Germany
    J Am Soc Nephrol 16:1501-11. 2005
    ..4; 95% confidence interval, 1.2 to 148; P = 0.034). A dominant role of the donor's ABCB1 genotype was identified for development of CsA nephrotoxicity. This suggests that P-glycoprotein is an important factor in CsA nephrotoxicity...
  64. ncbi request reprint Impact of CYP2B6 polymorphism on hepatic efavirenz metabolism in vitro
    Zeruesenay Desta
    Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, 1001 West 10th Street, WD Myers Bldg, W7123, Indianapolis, IN 46202, USA
    Pharmacogenomics 8:547-58. 2007
    ..To determine the influence of cytochrome P450 2B6 (CYP2B6) genotype on the rate of oxidative efavirenz metabolism in human liver microsomes...
  65. ncbi request reprint Thiopurine methyltransferase (TPMT) genotype and early treatment response to mercaptopurine in childhood acute lymphoblastic leukemia
    Martin Stanulla
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    JAMA 293:1485-9. 2005
    ..Thiopurine methyltransferase (TPMT) is involved in the metabolism of mercaptopurine and subject to genetic polymorphism, with heterozygous individuals having intermediate and homozygous mutant individuals having very low TPMT activity...
  66. ncbi request reprint Contribution of CYP3A5 to the in vitro hepatic clearance of tacrolimus
    Landry K Kamdem
    Department of Clinical Pharmacology and Clinical Chemistry, Georg August University, Goettingen, Germany
    Clin Chem 51:1374-81. 2005
    ..Patients with high concentrations of CYP3A5, a CYP3A isoenzyme polymorphically produced in these organs, require higher doses of tacrolimus, but the exact mechanism of this association is unknown...
  67. ncbi request reprint Three haplotypes associated with CYP2A6 phenotypes in Caucasians
    Michael Haberl
    EPIDAUROS Biotechnologie AG, Bernried, Germany
    Pharmacogenet Genomics 15:609-24. 2005
    ..In summary A CYP2A6*1A-like allele, *9B and *12B are major genetic determinants of CYP2A6 phenotype variation in Caucasians...
  68. ncbi request reprint Genetic signature consistent with selection against the CYP3A4*1B allele in non-African populations
    Markus Schirmer
    Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany
    Pharmacogenet Genomics 16:59-71. 2006
    ..The elimination of CYP3A4*1B involved different parts of the CYP3A locus in European Caucasians and Asians. Because CYP3A4 is involved in the vitamin D metabolism, rickets may have been the underlying selecting factor...
  69. ncbi request reprint Transcriptional profiling of genes induced in the livers of patients treated with carbamazepine
    Mikael Oscarson
    Division of Pharmacology Neurobiology, Biozentrum, University of Basel, Basel, Switzerland
    Clin Pharmacol Ther 80:440-456. 2006
    ..The molecular mechanisms underlying this response are not well understood, however, and the spectrum of CBZ-inducible genes in human liver has not been thoroughly investigated...
  70. ncbi request reprint Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter expression in human liver
    Yvonne Meier
    Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital, Zurich, Switzerland
    Hepatology 44:62-74. 2006
    ..Furthermore, data suggest a polymorphic transporter expression pattern, which might constitute a risk factor for the development of acquired forms of cholestatic liver diseases...
  71. ncbi request reprint Cytochrome P450 2B6 activity as measured by bupropion hydroxylation: effect of induction by rifampin and ethnicity
    Katarzyna K Loboz
    Faculty of Pharmacy, University of Sydney, Sydney, Australia
    Clin Pharmacol Ther 80:75-84. 2006
    ....
  72. ncbi request reprint Functional study of the 830C>G polymorphism of the human carboxylesterase 2 gene
    Ricardo Bellott
    Laboratoire de Pharmacologie des Agents Anticancéreux, Institut Bergonie, Universite Victor Segalen Bordeaux 2, France
    Cancer Chemother Pharmacol 61:481-8. 2008
    ....
  73. doi request reprint 6-mercaptopurine and 9-(2-phosphonyl-methoxyethyl) adenine (PMEA) transport altered by two missense mutations in the drug transporter gene ABCC4
    Daniel Janke
    Institute of Pharmacology, University of Mainz, Mainz, Germany
    Hum Mutat 29:659-69. 2008
    ..Our study shows that Xenopus oocytes are well suited to characterize MRP4 and its protein variants. Carriers of the rare MRP4 variants Y556C and V776I may have altered disposition of MRP4 substrates...
  74. ncbi request reprint GSTP1 and MDR1 genotypes and central nervous system relapse in childhood acute lymphoblastic leukemia
    Martin Stanulla
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Int J Hematol 81:39-44. 2005
    ..These results suggested a modulating role for host genetic variation in the development of CNS relapse in childhood ALL treated according to Berlin-Frankfurt-Münster protocols...