Titre
Influence of ABCB1, ABCC1, ABCC2, and ABCG2 haplotypes on the cellular exposure of nelfinavir in vivo
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Colombo, S.
Auteure/Auteur
Soranzo, N.
Auteure/Auteur
Rotger, M.
Auteure/Auteur
Sprenger, R.
Auteure/Auteur
Bleiber, G.
Auteure/Auteur
Furrer, H.
Auteure/Auteur
Buclin, T.
Auteure/Auteur
Goldstein, D.
Auteure/Auteur
Decosterd, L.
Auteure/Auteur
Telenti, A.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1744-6872
Statut éditorial
Publié
Date de publication
2005-09
Volume
15
Numéro
9
Première page
599
Dernière page/numéro d’article
608
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep
Research Support, Non-U.S. Gov't --- Old month value: Sep
Résumé
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> AUCCT > AUCTT (ratio 2.4, 1.3, 1, Ptrend=0.006). Haplotypic analysis using tagging SNPs did not improve the single SNP association values.
Sujets
PID Serval
serval:BIB_B3A8434770B5
PMID
Date de création
2008-01-25T09:51:20.441Z
Date de création dans IRIS
2025-05-21T04:56:17Z