Polymorphisms of tenofovir disoproxil fumarate transporters and risk of kidney tubular dysfunction in HIV-positive patients: genetics of tenofovir transporters.

Overview

The association between single nucleotide polymorphisms of genes encoding transport proteins involved in the bio-disposition of tenofovir disoproxil fumarate (TDF) and kidney tubular dysfunction (KTD) in HIV-positive patients was examined in this study. Fifty-eight patients who received TDF were screened for KTD using retinol-binding protein (RBP) concentration in urine. We defined KTD as the top quartile of urinary RBP/creatinine ratio (>17 μg/mmol), regardless of estimated glomerular filtration rate (eGFR) or proteinuria. Genotyping of genes encoding transport proteins involved in the disposition of TDF was undertaken using validated Taqman 5' nuclease assays. Patients with KTD (N = 15) had higher current CD4 cell counts, lower eGFR and were less likely to possess the genotype CC at position 24 of the ABBC2 (MRP2, rs717620) gene. In multivariate analysis, genotype CC at position 24 of the ABBC2 gene was significantly associated with KTD (odds ratio =0.05, 95% confidence interval = 0.003-0.7, P = 0.027). Genotype CC at position 24 of the ABBC2 (MRP2 rs717620) gene was significantly associated with a reduced risk of elevated urinary RBP in HIV-positive patients exposed to TDF.