ABCC4 single-nucleotide polymorphisms as markers of tenofovir disoproxil fumarate-induced kidney impairment

Cheli, Stefania; Baldelli, Sara; Silvestri, Annalisa De; Fusi, Marta; Minisci, Davide; Gervasoni, Cristina; Cattaneo, Dario; Clementi, Emilio; Meraviglia, Paola; Montrasio, Cristina

doi:10.1038/s41397-021-00235-7

Cited by 8 publications

(6 citation statements)

References 27 publications

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“…Contrastingly, researched polymorphisms in the ABCC4 gene show less dissimilarity in results. Cheli et al found a significant association with the ABCC4 rs3742106 G allele and decrement in estimated GFR, as well as the increase in the mean TDF plasma concentration and TDF discontinuation for toxicity, in line with a previous study by Rungtivasuwan et al who also observed a 30% increase in the mean TDF plasma concentration in Thai HIV-infected patients with rs3742106 TG/GG genotype [18,20]. This variant may be associated with a reduced expression and/ or function of the transporter [19].…”

Section: Introductionsupporting

confidence: 67%

“…Cheli et al also suggested that c. 3348 AA genotype in ABCC4 rs1751034 was associated with higher TDF plasma concentrations, which was in line with the study result by Rungtivasuwan et al (n=342) who showed lower oral clearance for AA genotype, but at position c. 3463 [18,22]. This result was in disagreement with the previous study by Rungtivasuwan et al, as well as by Kiser et al where G allele was mentioned instead, however, those studies were carried out on smaller patient groups (n=150 and n=30, respectively) [20,23].…”

Section: Introductionsupporting

confidence: 67%

“…Polymorphism in the ABCC10 gene (encoding MRP 7) c. 1875+526G>A (rs9349256) is also a marker of renal impairment. In the same study by Cheli et al allele G was carried more frequently by those patients who had an annual eGFR decrement >5 mL/min/1.73 m 2 , and the main risk factor resulted to be body mass index (BMI), eGFR, and concurrent use of protease inhibitors (PIs) [18]. ABCC10 rs2125739 C allele has been associated with significantly lower plasma concentrations of NVP in White HIV+ patients, and therefore, lower effectiveness [25].…”

Section: Introductionmentioning

confidence: 97%

“…There are conflicting results on whether a possession of rs717620 and rs2273697 SNPs correlates with pre-existing tubular dysfunction in patients or not [17]. Recent research of these SNPs in 179 patients in Milan reported a lack of association of ABCC2 with TDFinduced kidney impairment [18]. Another large study on the Japanese population (n=703) carried out on treatment-naïve Japanese HIV-1-infected patients reported that rs717620 (C/C) and rs2273697 (A/A) were not associated with TDF-induced nephrotoxicity [19].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacogenetic effects of single nucleotide polymorphisms commonly associated with antiretroviral therapy metabolism

Bazhenova

Миронов

et al. 2022

VIČ-infekc. immunosupr.

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Introduction. Identification of pharmacogenetic effects on antiretroviral therapy (ART) has become an important milestone to reach in the advancement of personalised treatment for HIV-positive patients. The therapy schemes are accompanied by multiple side effects. Therapy effectiveness and adverse reactions can be dictated by individual genetic predisposition factors, which should be taken into account for an optimal prescription. Some genetic markers (HLA-B*57:01 and UGT1A1*28), were already proven to improve discontinuation rates, and efforts are allocated to expand the range of clinically-relevant genetic tests.Objective. In this review, an updated summary of genetic polymorphisms and their effects defining patients’ tolerability to ART is presented. The aim of this research is to assess single nucleotide polymorphisms (SNPs) present in the genes that encode proteins involved in ART metabolism and transport. This review will be used to develop a PCR-based testing methodology for the detection and confirmation of risk alleles in the Caucasian population.Materials and methods. Data from 46 original research papers and reviews was analysed. Allele frequencies of the most relevant polymorphisms were checked against the data for European population.Results. As an outcome of this review, a few most promising SNPs were selected for future research. Firstly, ABCC4 rs1751034 and rs3742106 and ABCC10 rs9349256 and rs2125739 were associated with an increased risk of renal impairment, higher plasma concentration, and toxicity when treated with tenofovir. Parallel analysis of ABCC4 and ABCC10 SNP effects on renal impairment together with CYP24A1 rs2248359 that was recently reported as a potential renal toxicity marker might be more informative. Secondly, CYP2B6 rs3745274 that was associated with an increased efavirenz plasma concentration, and increased risk of liver and CNS toxicity should be evaluated. SNPs in CYP2B6, CYP2A6 (rs28399433), and CYP3A4 (rs4646437) should be evaluated in parallel since possession of all three variants might put patients at a much higher risk.Conclusion. Identified alleles could become new markers used in drug prescription protocols if significant effect in Caucasian population will be found. The most relevant SNPs should be tested in in supporting future studies to evaluate the significance for patients with HIV in Russia.

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Section: Introductionsupporting

confidence: 67%

Section: Introductionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacogenetic effects of single nucleotide polymorphisms commonly associated with antiretroviral therapy metabolism

Bazhenova

Миронов

et al. 2022

VIČ-infekc. immunosupr.

View full text Add to dashboard Cite

show abstract

“…Polymorphisms in genes such as ABCC2 , ABCC4 and ABCC10 that encode proximal tubule transporters involved in tenofovir clearance may play a role in tenofovir accumulation and the risk of renal injury; however, findings to date have been inconsistent. A retrospective study using real-world clinical data in Italy found a significant association between variants in ABCC4 and clinical outcomes associated with tenofovir toxicity, as well as a predictive role of ABCC10 genetic variants [16].…”

Section: Nucleoside/nucleotide Reverse Transcriptase Inhibitorsmentioning

confidence: 99%

Renal adverse drug reactions

Hughes¹

2021

Current Opinion in HIV and AIDS

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Purpose of review Chronic kidney disease (CKD) is common in people living with HIV (PLWH) and is related to a multitude of factors. The aim of this review is to provide an overview of the most recent evidence of renal adverse effects of antiretroviral drugs, predictors of CKD risk and areas for future research. Recent findingsAdvancing age, cardiometabolic risk factors and adverse effects of antiretroviral drugs contribute to the higher prevalence of CKD in PLWH. Genetic factors and baseline clinical CKD risk are strongly correlated to risk of incident CKD, although it is unclear to what extent gene polymorphisms explain renal adverse effects related to tenofovir disoproxil fumarate (TDF). Switching from TDF to tenofovir alafenamide (TAF) in people with baseline renal dysfunction improves renal parameters; however, the long-term safety and benefit of TAF in individuals at low risk of CKD is an area of ongoing research.

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Pathophysiological and Genetic Basis of Tenofovir-Induced Acute Renal Dysfunction: Strategies and Recent Developments for Better Clinical Outcomes

et al. 2022

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ABCC4 single-nucleotide polymorphisms as markers of tenofovir disoproxil fumarate-induced kidney impairment

Cited by 8 publications

References 27 publications

Pharmacogenetic effects of single nucleotide polymorphisms commonly associated with antiretroviral therapy metabolism

Pharmacogenetic effects of single nucleotide polymorphisms commonly associated with antiretroviral therapy metabolism

Renal adverse drug reactions

Pathophysiological and Genetic Basis of Tenofovir-Induced Acute Renal Dysfunction: Strategies and Recent Developments for Better Clinical Outcomes

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