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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Influence of ABCB1, ABCC1, ABCC2, and ABCG2 haplotypes on the cellular exposure of nelfinavir in vivo
Pharmacogenetics and Genomics, Volume 15, No. 9, Year 2005
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Description
Objectives: The human immunodeficiency virus protease inhibitor nelfinavir is substrate of polyspecific drug transporters encoded by ABCB1 (P-glycoprotein), ABCC1 (MRP1) and ABCC2 (MRP2), and an inhibitor of BCRP, encoded by ABCG2. Genetic polymorphism in these genes may be associated with changes in transport function. Methods: A comprehensive evaluation of single nucleotide polymorphisms (39 SNPs in ABCB1, 7 in ABCC1, 27 in ABCC2, and 16 in ABCG2), and inferred haplotypes was done to assess possible associations of genetic variants with cellular exposure of nelfinavir in vivo. Analysis used peripheral mononuclear cells from individuals receiving nelfinavir (n = 28). Key results were re-examined in a larger sample size (n = 129) contributing data on plasma drug levels. Results and conclusions: There was no significant association between cellular nelfinavir area under the curve (AUC) and SNPs or haplotypes at ABCC1, ABCC2, ABCG2. There was an association with cellular exposure for two loci in strong linkage disequilibrium: ABCB1 3435C>T; AUCTT>AUCCT> AUCCC (ratio 2.1, 1.4, 1, Ptrend=0.01), and intron 26 +80T>C; AUCCC> AUC CT > AUCTT (ratio 2.4, 1.3, 1, Ptrend=0.006) . Haplotypic analysis using tagging SNPs did not improve the single SNP association values. © 2005 Lippincott Williams & Wilkins.
Authors & Co-Authors
Soranzo, Nicole
United Kingdom, London
University College London
Furrer, Hansjakob
Switzerland, Bern
University Hospital Bern
Buclin, Thierry J.
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Goldstein, David B.
United Kingdom, London
University College London
Décosterd, Laurent Arthur
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Telenti, Amalio
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Battegay, Manuel
Unknown Affiliation
Bernasconi, Enos
Unknown Affiliation
Böni, Jürg
Unknown Affiliation
Bucher, Heiner C.
Unknown Affiliation
Bürgisser, Ph
Unknown Affiliation
Cattacin, Sandro
Unknown Affiliation
Cavassini, Matthias L.
Unknown Affiliation
Dubs, Rolf W.
Unknown Affiliation
Egger, Matthias
Unknown Affiliation
Elzi, Luigia
Unknown Affiliation
Erb, Peter
Unknown Affiliation
Fischer, Marek
Unknown Affiliation
Flepp, Markus J.
Unknown Affiliation
Fontana, Adriano
Unknown Affiliation
Francioli, Patrick B.
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Gorgievski, Meri
Unknown Affiliation
Günthard, Hüldrych Fritz
Unknown Affiliation
Hirschel, Bernard J.
Unknown Affiliation
Kaiser, Laurent K.
Unknown Affiliation
Kind, Christian H.
Unknown Affiliation
Klimkait, Thomas
Unknown Affiliation
Ledergerber, Bruno
Unknown Affiliation
Opravil, Milos
Unknown Affiliation
Paccaud, Fred Michel
Unknown Affiliation
Pantaleo, Giuseppe P.
Unknown Affiliation
Perrin, Luc Henri
Unknown Affiliation
Piffaretti, Jean Claude L.
Unknown Affiliation
Rickenbach, Martin
Unknown Affiliation
Rudin, Christoph
Unknown Affiliation
Schmid, Patrick
Unknown Affiliation
Schüpbach, Jörg Rg
Unknown Affiliation
Speck, Roberto F.
Unknown Affiliation
Trkola, Alexandra
Unknown Affiliation
Vernazza, Pietro Luigi
Unknown Affiliation
Weber, Rainer
Unknown Affiliation
Yerly, Sabine T.B.D.
Unknown Affiliation
Statistics
Citations: 72
Authors: 42
Affiliations: 4
Identifiers
Doi:
10.1097/01.fpc.0000172241.42546.d3
ISSN:
17446872
Research Areas
Genetics And Genomics