1. Association between ABCC2 gene haplotypes and tenofovir-induced proximal tubulopathy.
- Author
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Izzedine H, Hulot JS, Villard E, Goyenvalle C, Dominguez S, Ghosn J, Valantin MA, Lechat P, and Deray AG
- Subjects
- Adenine adverse effects, Adult, Aged, Case-Control Studies, Female, Gene Frequency, Genetic Predisposition to Disease, HIV Infections complications, Humans, Male, Middle Aged, Multidrug Resistance-Associated Protein 2, Point Mutation, Polymorphism, Single Nucleotide, Statistics as Topic, Tenofovir, Adenine analogs & derivatives, Anti-HIV Agents adverse effects, Fanconi Syndrome chemically induced, Fanconi Syndrome genetics, HIV Infections drug therapy, Haplotypes, Membrane Transport Proteins genetics, Multidrug Resistance-Associated Proteins genetics, Organophosphonates adverse effects
- Abstract
Background: Tenofovir 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., Methods: Mutational 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., Results: Six 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<.02). ABCC2 haplotypes were significantly associated with the onset of TDF-induced rPT--CATC appeared to be a predisposing haplotype, as it was found in 40.9% of the group 1 case patients and in 13.7% of the group 2 control subjects (P<.01), whereas CGAC appeared to be a protective haplotype, as it was not observed in the group 1 case patients but was present in 20.2% of the group 2 control subjects (P<.01). No association was observed between ABCC4 polymorphism and TDF-induced rPT in the present study., Conclusion: ABCC2 haplotypes are associated with rPT induced by TDF in HIV-1-infected patients.
- Published
- 2006
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