Pharmakogenetik von Transmembrantransportern

Glossar

ABC ATP-binding-cassette

Allel Zustandsform eines Genorts

Carrier Transporter

CNT Concentrative nucleoside transporter

ENT Equilibrative nucleoside transporter

Exon kodierende DNA-Teilsequenz eines Gens

Genotyp bestimmte Allelkonfiguration an einem Genlocus

Haplotyp einem Chromosom zuzuordnende Allelkombination eines Genlocus

Heterozygot Verschiedene Allele auf beiden Chromosomen

Homozygot Identische Allele auf beiden Chromosomen

Intron nicht-kodierende DNA-Teilsequenz eines Gens, die Exons unterbricht

Kodierend Veränderung der Nukleotidsequenz einer DNA, die zu einem Aminosäureaustausch führt

MDR1 Multidrug resistance gene, Typ 1

MRP Multidrug resistance related protein

Nicht-kodierend Veränderung der Nukleotidsequenz einer DNA, die zu keinem Aminosäureaustausch führt

OATP Organic anion transporting protein, transportiert organische Anionen

OCT Organic cation transporter, transportiert organische Kationen

PEPT Proton/peptide cotransporter

PEPT1-RF Durch alternatives Splicing entstandenes verwandtes Fragment des PEPT1

Pgp P-Glykoprotein, Genprodukt des MDR1

Polymorphismus Häufig vorkommende Variation (mind. 1 % Prävalenz) eines Gens

Promotor Bindungsstelle für Regulatoren, am Anfang der DNA eines Gens gelegen

SLC Solute Carrier

SNP Single nucleotide polymorphism, Einzelbasenaustausch innerhalb eines Gens

Splice-Variante Durch Kombination nicht aufeinander folgender Exons eines Gens entstandenes alternatives Protein

Splicing Prozess, in dem Introns aus dem primären RNA-Transkript eukaryotischer Gene entfernt werden

UAW Unerwünschte Arzneimittelwirkung

Literatur

• 1 Arndt P, Volk C, Gorboulev V. et al . Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1.  Am J Physiol Renal Physiol. 2001;  281 110-115
• 2 Cascorbi I, Gerloff T, Johne A. et al . Frequency of single nucleotide polymorphisms (SNPs) in the P-glycoprotein drug transporter MDR1 gene in Caucasians.  Clin Pharmacol Ther. 2001;  69 169-174
• 3 Cordon-Cardo C, O’Brien J P, Boccia J, Casals D, Bertino J R, Melamed M R. Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues.  J Histochem Cytochem. 1990;  38 1277-1287
• 4 Dresser M J, Leabman M K, Giacomini K M. Transporters involved in the elimination of drugs in the kidney: organic anion transporters and organic cation transporters.  J Pharm Sci. 2001;  90 397-421
• 5 Fei Y J, Liu W, Prasad P D. et al . Identification of the histidyl residue obligatory for the catalytic activity of the human H+/peptide cotransporters PEPT1 and PEPT2.  Biochemistry. 1997;  36 452-460
• 6 Fellay J, Marzolini C, Meaden E R. et al . Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study.  Lancet. 2002;  359 30-36
• 7 Ganapathy M E, Brandsch M, Prasad P D, Ganapathy V, Leibach F H. Differential recognition of beta-lactam antibiotics by intestinal and renal peptide transporters, PEPT 1 and PEPT 2.  J Biol Chem. 1995;  270 25 672-25 677
• 8 Gao M, Yamazaki M, Loe D W. et al . Multidrug resistance protein. Identification of regions required for active transport of leukotriene C4.  J Biol Chem. 1998;  273 10 733-10 740
• 9 Gerloff T, Schaefer M, Johne A. et al . MDR1 genotypes do not influence the absorption of a single oral dose of 1 mg digoxin in healthy white males.  Br J Clin Pharmacol. 2002;  54 610-616
• 10 Goettler M, Schneeweiss S, Hasford J. Adverse drug reaction monitoring - cost and benefit considerations part II: cost and preventability of adverse drug reactions leading to hospital admission.  Pharmacoepidemiol Drug Safety. 1997;  6 S79-90 (Suppl 3)
• 11 Gorboulev V, Ulzheimer J C, Akhoundova A. et al . Cloning and characterization of two human polyspecific organic cation transporters.  DNA Cell Biol. 1997;  16 871-881
• 12 Greiner B, Eichelbaum M, Fritz P. et al . The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin.  J Clin Invest. 1999;  104 147-153
• 13 Gründemann D. et al . Drug excretion mediated by a new prototype of polyspecific transporter.  Nature. 1994;  372 549-552
• 14 Han H, de Vrueh R L, Rhie J K. et al . 5’-Amino acid esters of antiviral nucleosides, iacyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter.  Pharm Res. 1998;  15 1154-1159
• 15 Hipfner D R, Mao Q, Qiu W. et al . Monoclonal antibodies that inhibit the transport function of the 190-kDa multridrug resistance protein, MRP.  J Biol Chem. 1999;  274 15 420-15 426
• 16 Hoffmeyer S, Burk O, von Richter O. et al . Functional polymorphisms of the human multidrug resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo.  Proc Natl Acad Sci USA. 2000;  97 3473-3478
• 17 Hu M, Zheng L, Chen J. et al . Mechanisms of transport of quinapril in Caco-2 cell monolayers: comparison with cephalexin.  Pharm Res. 1995;  12 1120-1125
• 18 Ito S, Ieiri I, Tanabe M, Suzuki A, Higuchi S, Otsubo K. Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects.  Pharmacogenetics. 2001;  11 175-184
• 19 Itoda M, Saito Y, Soyama A. et al . Polymorphisms in the ABCC2 (cMOAT/MRP2) gene found in 72 established cell lines derived from Japanese individuals: an association between single nucleotide polymorphisms in the 5’-untranslated region and exon 28.  Drug Metab Dispos. 2002;  30 363-364
• 20 Johne A, Kopke K, Gerloff T. et al . Modulation of steady-state kinetics of digoxin by haplotypes of the P-glycoprotein MDR1 gene.  Clin Pharmacol Ther. 2002;  72 584-594
• 21 Juranka P F, Zastawny R L, Ling V. P-glykoprotein: multidrug-resistance and a superfamily of membrane-associated transport proteins.  FASEB J. 1989;  3 2583-2592
• 22 Kerb R, Brinkmann U, Chatskaia N. et al . Identification of genetic variations of the human organic cation transporter hOCT1 and their functional consequences.  Pharmacogenetics. 2002;  12 591-595
• 23 Kim R B, Leake B F, Choo E F. et al . Identification of functionally variant MDR1 alleles among European Americans and African Americans.  Clin Pharmacol Ther. 2001;  70 189-199
• 24 Koepsell H. Organic cation transporters in intestine, kidney, liver, and brain.  Annu Rev Physiol. 1998;  60 243-266
• 25 Lazarou J, Bruce H, Pomeranz H, Corey P N. Incidence of adverse drug reactions in hospitalised patients.  JAMA. 1998;  279 1200-1205
• 26 Mizutani T. PM frequencies of major CYPs in Asian and Caucasians.  Drug Metab Rev. 2003;  35 99-106
• 27 Nishizato Y, Suzuki H, Kimura M. et al . Polymorphisms of OATP-C (SCL21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics.  Clin Pharmacol Ther. 2003;  73 554-565
• 28 Nozawa T, Nakajima M, Tamai I. et al . Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allelic frequencies in the Japanese population and functional analysis.  J Pharmacol Exp Ther. 2002;  302 804-813
• 29 Paulusma C C, Oude Elferink R P. The canalicular multispecific organic anion transporter and conjugated hyperbilirubinemia in rat and man.  J Mol Med. 1997;  75 420-428
• 30 Rao V V, Dahlheimer J L, Bardgett M E. et al . Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal-fluid drug-permeability barrier.  Proc Natl Acad Sci USA. 1999;  96 3900-3905
• 31 Roots I, Brockmoller J. Pharmakogenetik. 3rd ed Darmstadt: Steinkopff In: Rietbrock N, Staib AH, Loew D, editors. Klinische Pharmakologie 1996: 101-120
• 32 Saito H, Motohashi H, Mukai M, Inui K. Cloning and characterization of a pH-sensing regulatory factor that modulates transport activity of the human H+/paptide cotransporter, PEPT1.  Biochem Biophys Res Commun. 1997;  237 557-582
• 33 Sakaeda T, Nakamura T, Horinouchi M. et al . MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects.  Pharm Res. 2001;  18 1400-1404
• 34 Siddiqui A, Kerb R, Weale M E. et al . Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1.  N Engl J Med. 2003;  348 1442-1448
• 35 Siegmund W, Ludwig K, Giessmann T. et al . The effects of the human MDR1 genotype on the expression of duodenal P-glycoprotein and disposition of the probe drug talinolol.  Clin Pharmacol Ther. 2002;  72 572-583
• 36 Steijns L S, Van Der Weide J. Ultrarapid drug metabolism: PCR-based detection of CYP2D6 gene duplication.  Clin Chem. 1998;  44 914-917
• 37 Su S F, Huang J D. Inhibition of the intestinal digoxin absorption and exsorption by quinidine.  Drug Metab Dispos. 1996;  24 142-147
• 38 Tanigawara Y. Role of P-glykoprotein in drug disposition.  Ther Drug Monit. 2000;  22 137-140
• 39 Temple C S, Boyd C A. Proton-coupled oligopeptide transport by rat renal cortical brush border membrane vesicles: a functional analysis using ACE inhibitors to determine the isoform of the transporter.  Biochim Biophys Acta. 1998;  1373 277-281
• 40 Terada T, Saito H, Mukai M, Inui K I. Identification of the histidine residues involved in substrate recognition by a rat H+/peptide cotransporter, PEPT1.  FEBS Lett. 1996;  394 196-200
• 41 Tirona R G, Leake B F, Merino G, Kim R B. Polymorphisms in OATP-C: Identification of multiple allelic variants associated with altered transport activity among European- and African-Americans.  J Biol Chem. 2001;  276 35 669-35 675
• 42 Urtti A, Johns S J, Sadee W. Genomic structure of proton-coupled oligopeptide transporter hPEPT1 and pH sensing regulatory splice variant.  AAPS Pharmsci. 2001;  3 1
• 43 Westphal K, Weinbrenner A, Giessmann T. et al . Oral bioavailability of digoxin is enhanced by talinolol: evidence for involvement of intestinal P-glycoprotein.  Clin Pharmacol Ther. 2000;  68 6-12