ArticleScientific reports2016
The independent contribution of miRNAs to the missing heritability in CYP3A4/5 functionality and the metabolism of atorvastatin.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- A comprehensive narrative review on precision medicine approach to hypertension: exploring the role of genetics, epigenetics, microbiome, and artificial intelligence.Journal of health, population, and nutrition · 2025Review
- CYP3A4*1B and CYP3A5*3 SNPs significantly impact the response of Egyptian candidates to high-intensity statin therapy to atorvastatin.European journal of medical research · 2024Article
- Novel Approaches to Characterize Individual Drug Metabolism and Advance Precision Medicine.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Association between CYP3A4/CYP3A5 genetic polymorphisms and treatment outcomes of atorvastatin worldwide: is there enough research on the Egyptian population?European journal of medical research · 2023Review
- The Roles of microRNAs in Cancer Multidrug Resistance.Cancers · 2022Review
- Genome-wide microRNA profiles identify miR-107 as a top miRNA associating with expression of the CYP3As and other drug metabolizing cytochrome P450 enzymes in the liver.Frontiers in pharmacology · 2022Article
- Microvesicles: the functional mediators in sorafenib resistance.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- 3D Adipose Tissue Culture Links the Organotypic Microenvironment to Improved Adipogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Article
- Effects ofPharmaceutical biology · 2019Article
- MicroRNAs and cancer drug resistance: over two thousand characters in search of a role.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Regulation of cytochrome P450 expression by microRNAs and long noncoding RNAs: Epigenetic mechanisms in environmental toxicology and carcinogenesis.Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews · 2019Article
- Effects of Danshen tablets on pharmacokinetics of atorvastatin calcium in rats and its potential mechanism.Pharmaceutical biology · 2018Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To evaluate the independent contribution of miRNAs to the missing heritability in CYP3A4/5 functionality and atorvastatin metabolism, the relationships among three levels of factors, namely (1) clinical characteristics, CYP3A4/5 genotypes, and miRNAs, (2) CYP3A4 and CYP3A5 mRNAs, and (3) CYP3A activity, as well as their individual impacts on atorvastatin metabolism, were assessed in 55 human liver tissues. MiR-27b, miR-206, and CYP3A4 mRNA respectively accounted for 20.0%, 5.8%, and 9.5% of the interindividual variations in CYP3A activity. MiR-142 was an independent contributor to the expressions of CYP3A4 mRNA (partial R(2) = 0.12, P = 0.002) and CYP3A5 mRNA (partial R(2) = 0.09, P = 0.005) but not CYP3A activity or atorvastatin metabolism. CYP3A activity was a unique independent predictor of variability of atorvastatin metabolism, explaining the majority of the variance in reduction of atorvastatin (60.0%) and formation of ortho-hydroxy atorvastatin (78.8%) and para-hydroxy atorvastatin (83.9%). MiR-27b and miR-206 were found to repress CYP3A4 gene expression and CYP3A activity by directly binding to CYP3A4 3'-UTR, while miR-142 was found to indirectly repress CYP3A activity. Our study indicates that miRNAs play significant roles in bridging the gap between epigenetic effects and missing heritability in CYP3A functionality.
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