OpenCYP: An open source database exploring human variability in activities and frequencies of polymophisms for major cytochrome P-450 isoforms across world populations
| Autor: | Laura Turco, Leonie S. Lautz, K. Darney, Jean-Lou Dorne, Emanuela Testai, Franca M. Buratti, Susanna Vichi, Emma Di Consiglio |
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| Přispěvatelé: | Istituto Superiore di Sanita [Rome], Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), European Food Safety Authority (EFSA), This project was supported by the European Food Safety Authority (EFSA) under the grant agreement no. GA/EFSA/SCER/2015/01. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Proteomics CYP2D6 PBK models Metabolite [SDV]Life Sciences [q-bio] Cytochrome P450 Biology Toxicology computer.software_genre Genetic polymorphisms 030226 pharmacology & pharmacy Human variability 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cytochrome P-450 Enzyme System Databases Genetic MESH: Polymorphism Genetic medicine Humans Protein Isoforms CYP2A6 CYP3A7 MESH: Databases Genetic Aged Risk assessment Aged 80 and over Polymorphism Genetic Enzymatic activity CYP3A4 Database CYP1A2 General Medicine Dextromethorphan Middle Aged chemistry Population Surveillance 030220 oncology & carcinogenesis MESH: Cytochrome P-450 Enzyme System Female computer medicine.drug |
| Zdroj: | Toxicology Letters Toxicology Letters, Elsevier, 2021, ⟨10.1016/j.toxlet.2021.07.019⟩ |
| ISSN: | 0378-4274 |
| Popis: | International audience; The open source database "OpenCYP database" has been developed based on the results of extensive literature searches from the peer-reviewed literature. OpenCYP provides data on human variability on baseline of activities and polymophism frequencies for selected cytochrome P-450 isoforms (CYP1A2, CYP2A6, CYP2D6, CYP3A4/3A5 and CYP3A7) in healthy adult populations from world populations. CYP enzymatic activities were generally expressed as the metabolic ratio (MR) between an unchanged probe drug and its metabolite(s) in urine or plasma measured in healthy adults. Data on other age groups were very limited and fragmented, constituting an important data gap. Quantitative comparisons were often hampered by the different experimental conditions used. However, variability was quite limited for CYP1A2, using caffeine as a probe substrate, with a symmetrical distribution of metabolic activity values. For CYP3A4, human variability was dependent on the probe substrate itself with low variability when data considering the dextromethorphan/demethilathed metabolite MR were used and large variability when the urinary 6β-hydroxycortisol/cortisol ratio was used. The largest variability in CYP activity was shown for CYP2D6 activity, after oral dosing of dextromethorphan, for which genetic polymorphisms are well characterised and constitute a significant source of variability. It is foreseen that the OpenCYP database can contribute to promising tools to support the further development of QIVIVE and PBK models for human risk assessment of chemicals particularly when combined with information on isoform-specific content in cells using proteomic approaches. |
| Databáze: | OpenAIRE |
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