ArticlePharmacogenetics and genomics2015
A pharmacogenetic candidate gene study of tenofovir-associated Fanconi syndrome.
Article in Pharmacogenetics and genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Trial
- Pharmacogenetic Analysis of the Model-Based Pharmacokinetics of Five Anti-HIV Drugs: How Does This Influence the Effect of Aging?Clinical and translational science · 2018Trial
- An Exploratory Pharmacogenetic Pilot Study of Two Reverse Transcriptase Inhibitors, Tenofovir Alafenamide Fumarate and Tenofovir Disoproxil Fumarate.Drugs in R&D · 2025Article
- ABCC4 single-nucleotide polymorphisms as markers of tenofovir disoproxil fumarate-induced kidney impairment.The pharmacogenomics journal · 2021Article
- The genetic polymorphisms of XPR1 and SCL34A3 are associated with Fanconi syndrome in Chinese patients of tumor-induced osteomalacia.Journal of endocrinological investigation · 2021Article
- Pharmacogenetic determinants of kidney-associated urinary and serum abnormalities in antiretroviral-treated HIV-positive patients.The pharmacogenomics journal · 2020Article
- Article
- Article
- Reduced Kidney Function in Tenofovir Disoproxil Fumarate Based Regimen and Associated Factors: A Hospital Based Prospective Observational Study in Ethiopian Patients.International journal of nephrology · 2019Article
- Molecular Mechanisms for Species Differences in Organic Anion Transporter 1, OAT1: Implications for Renal Drug Toxicity.Molecular pharmacology · 2018Article
- Evaluating the association of single-nucleotide polymorphisms with tenofovir exposure in a diverse prospective cohort of women living with HIV.The pharmacogenomics journal · 2018Article
- Renal Drug Transporters and Drug Interactions.Clinical pharmacokinetics · 2017Review
- Reversal of Proximal Renal Tubular Dysfunction after Nucleotide Analogue Withdrawal in Chronic Hepatitis B.BioMed research international · 2017Article
- Data on single-step purification method for dye-labeled DNA sequencing.Data in brief · 2016Article
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundTenofovir disoproxil fumarate (TDF) is a widely used antiretroviral agent with favorable efficacy, safety, and tolerability profiles. However, renal adverse events, including the rare Fanconi syndrome (FS), may occur in a small subset of patients treated for HIV infections.
objectivesThe aim of this study was to identify genetic variants that may be associated with TDF-associated FS (TDF-FS).
methodsDNA samples collected from 19 cases with TDF-FS and 36 matched controls were sequenced, and genetic association studies were conducted on eight candidate genes: ATP-binding cassette (ABC) transporters ABCC2 (MRP2) and ABCC4 (MRP4), solute carrier family members SLC22A6 (OAT1) and SLC22A8 (OAT3), adenylate kinases 2 (AK2) and 4 (AK4), chloride transporter CIC-5 CLCN5, and Lowe syndrome protein OCRL. The functional effects of a single nucleotide polymorphism (SNP) predicted to alter the transport of tenofovir were then investigated in cells expressing an identified variant of ABCC4.
resultsThe case group showed a trend toward a higher proportion of rare alleles. Six SNPs in ABCC2 (three SNPs), ABCC4 (one SNP), and OCRL (two SNPs) were associated with TDF-FS case status; however, this association did not remain significant after correction for multiple testing. Six SNPs, present in OCRL (four SNPs) and ABCC2 (two SNPs), were significantly associated with increased serum creatinine levels in the cases, and this association remained significant after multiple test correction (P < 2 × 10). One synonymous SNP in ABCC2 (rs8187707, P = 2.10 × 10, β = -73.3 ml/min/1.73 m(2)) was also significantly associated with the decreased estimated glomerular filtration rate of creatinine among cases. However, these results were driven by rare SNPs present in a small number of severely affected cases. Finally, a previously uncharacterized, nonsynonymous SNP, rs11568694, that was predicted to alter MRP4 function had no significant effect on tenofovir cellular accumulation in vitro.
conclusionAlthough no single predictive genetic marker for the development of TDF-FS was identified, the findings from our study suggest that rare variants in multiple genes involved in the renal handling of tenofovir, and/or renal cell homeostasis, may be associated with increased susceptibility to TDF-FS.
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