Association between ABCC2 Gene Haplotypes and Tenofovir-Induced Proximal Tubulopathy

BackgroundTenofovir disoproxil fumarate (TDF) may induce renal proximal tubulopathy (rPT). There are no data on pharmacogenomic predictors of rPT in the genes encoding the multidrug-resistance protein (MRP) 2 and MRP4 transporters MethodsMutational screening of the genes for MRP2 (ABCC2) and MRP4 (A...

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Bibliographic Details
Published in:The Journal of infectious diseases 2006-12, Vol.194 (11), p.1481-1491
Main Authors: Izzedine, Hassane, Hulot, Jean-Sebastien, Villard, Eric, Goyenvalle, Catherine, Dominguez, Stephanie, Ghosn, Jade, Valantin, Marc Antoine, Lechat, Philippe, Deray, and Gilbert
Format: Article
Language:English
Subjects:
Adenine - adverse effects
Adenine - analogs & derivatives
Adult
Aged
AIDS
Alleles
Anti-HIV Agents - adverse effects
Antivirals
Case-Control Studies
Exons
Fanconi Syndrome - chemically induced
Fanconi Syndrome - genetics
Female
Gene Frequency
Genetic mutation
Genetic Predisposition to Disease
Genotypes
Haplotypes
HIV 1
HIV Infections - complications
HIV Infections - drug therapy
HIV/AIDS
Human immunodeficiency virus 1
Humans
Male
Medical genetics
Membrane Transport Proteins - genetics
Middle Aged
Multidrug Resistance-Associated Proteins - genetics
Nephrotoxicity
Organophosphonates - adverse effects
Point Mutation
Polymorphism, Single Nucleotide
Statistics as Topic
Tenofovir
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Summary:BackgroundTenofovir disoproxil fumarate (TDF) may induce renal proximal tubulopathy (rPT). There are no data on pharmacogenomic predictors of rPT in the genes encoding the multidrug-resistance protein (MRP) 2 and MRP4 transporters MethodsMutational screening of the genes for MRP2 (ABCC2) and MRP4 (ABCC4) was performed using genomic DNA from 13 human immunodeficiency virus type 1 (HIV-1)–infected patients (group 1) presenting with TDF-induced rPT. Concomitantly, 17 unrelated HIV-1–infected patients who had received TDF therapy and who did not have rPT (group 2) were included in a case-control analysis, to assess the influence of single-nucleotide polymorphisms (SNPs) identified in ABCC2 and ABCC4 ResultsSix SNPs were identified in ABCC2. A significant allelic association between the 1249 G→A SNP and TDF-induced rPT was observed (odds ratio, 6.11 [95% confidence interval, 1.19–31.15]; P
ISSN:0022-1899
1537-6613
DOI:10.1086/508546