ArticleBMC medical genetics2014
Analysis of single-nucleotide polymorphisms (SNPs) in human CYP3A4 and CYP3A5 genes: potential implications for the metabolism of HIV drugs.
Article in BMC medical genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- Population approach to analyze the pharmacokinetics of free and total lopinavir in HIV-infected pregnant women and consequences for dose adjustment.Antimicrobial agents and chemotherapy · 2015Trial
- Link between physical activity, nutrition, and antimicrobial pharmacokinetics and therapeutic efficacy: Implications for resistance management.SAGE open medicine · 2026Review
- A Bayesian approach for investigating the pharmacogenetics of combination antiretroviral therapy in people with HIV.Biostatistics (Oxford, England) · 2024Article
- Mechanisms and molecular targets surrounding the potential therapeutic effects of psychedelics.Molecular psychiatry · 2023Review
- Bidirectional Associations among Nicotine and Tobacco Smoke, NeuroHIV, and Antiretroviral Therapy.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Repurposing Drugs for COVID-19: Pharmacokinetics and Pharmacogenomics of Chloroquine and Hydroxychloroquine.Pharmacogenomics and personalized medicine · 2020Review
- Pharmacokinetics and pharmacodynamics of cytochrome P450 inhibitors for HIV treatment.Expert opinion on drug metabolism & toxicology · 2019Review
- Effects of Carbamazepine and Valproate on Serum Aspartate Aminotransferase, Alanine Aminotransferase and Gamma - Glutamyltransferase in Children.Medical archives (Sarajevo, Bosnia and Herzegovina) · 2017Article
- Article
- Pharmacogenetics of unboosted atazanavir in HIV-infected individuals in resource-limited settings: a sub-study of the AIDS Clinical Trials Group (ACTG) PEARLS study (NWCS 342).The Journal of antimicrobial chemotherapy · 2016Article
- Potential implications of CYP3A4, CYP3A5 and MDR-1 genetic variants on the efficacy of Lopinavir/Ritonavir (LPV/r) monotherapy in HIV-1 patients.Journal of the International AIDS Society · 2014Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDrug metabolism via the cytochrome P450 (CYP450) system has emerged as an important determinant in the occurrence of several drug interactions (adverse drug reactions, reduced pharmacological effect, drug toxicities). In particular, CYP3A4 and CYP3A5 (interacting with more than 60% of licensed drugs) exhibit the most individual variations of gene expression, mostly caused by single nucleotide polymorphisms (SNPs) within the regulatory region of the CYP3A4 and CYP3A5 genes which might affect the level of enzyme production.In this study, we sought to improve the performance of sensitive screening for CYP3A polymorphism detection in twenty HIV-1 infected patients undergoing lopinavir/ritonavir (LPV/r) monotherapy.
methodsThe study was performed by an effective, easy and inexpensive home-made Polymerase Chain Reaction Direct Sequencing approach for analyzing CYP3A4 and CYP3A5 genes which can detect both reported and unreported genetic variants potentially associated with altered or decreased functions of CYP3A4 and CYP3A5 proteins. Proportions and tests of association were used.
resultsAmong the genetic variants considered, CYP3A4*1B (expression of altered function) was only found in 3 patients (15%) and CYP3A5*3 (expression of splicing defect) in 3 other patients (15%). CYP3A5*3 did not appear to be associated with decreased efficacy of LPV/r in any patient, since none of the patients carrying this variant showed virological rebound during LPV/r treatment or low levels of TDM. In contrast, low-level virological rebound was observed in one patient and a low TDM level was found in another; both were carrying CYP3A4*1B.
conclusionsOur method exhibited an overall efficiency of 100% (DNA amplification and sequencing in our group of patients). This may contribute to producing innovative results for better understanding the inter-genotypic variability in gene coding for CYP3A, and investigating SNPs as biological markers of individual response to drugs requiring metabolism via the cytochrome P450 system.
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