ArticleThe Journal of pharmacology and experimental therapeutics2017
Predictors of Variation in CYP2A6 mRNA, Protein, and Enzyme Activity in a Human Liver Bank: Influence of Genetic and Nongenetic Factors.
Article in The Journal of pharmacology and experimental therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- Age (juvenile to aged) and sex effects on in vitro CYP2A6 enzyme activity in African green monkeys using nicotine and coumarin.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Pharmacokinetic Evaluation of a Cinnamon Product on CYP2A6 Substrate Drugs: Application of a Novel Tool Involving the Nicotine Metabolite Ratio.Clinical pharmacology and therapeutics · 2026Article
- Anesthesia-Informed Approaches to Insomnia: Shared Neural Circuits, Biomimetic Sleep, and Emerging Interventional Strategies.Nature and science of sleep · 2026Review
- Extending Investigations of miR-126-5p on the Regulation of CYP2A6, the Major Nicotine-Inactivating Enzyme.Pharmacology research & perspectives · 2025Article
- PharmVar GeneFocus: CYP2A6.Clinical pharmacology and therapeutics · 2024Review
- Cytochrome P450 FamilyACS pharmacology & translational science · 2024Article
- Review
- Quantitative Proteomics in Translational Absorption, Distribution, Metabolism, and Excretion and Precision Medicine.Pharmacological reviews · 2022Review
- Gender Differences in Smoking Initiation and Cessation Associated with the Intergenerational Transfer of Smoking across Three Generations: The Nagahama Study.International journal of environmental research and public health · 2022Article
- Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes.Clinical and translational science · 2022Article
- Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke.Clinical and translational science · 2021Article
- Characterization of CYP3A pharmacogenetic variation in American Indian and Alaska Native communities, targeting CYP3A4*1G allele function.Clinical and translational science · 2021Observational
- Tissue-Specific Proteomics Analysis of Anti-COVID-19 Nucleoside and Nucleotide Prodrug-Activating Enzymes Provides Insights into the Optimization of Prodrug Design and Pharmacotherapy Strategy.ACS pharmacology & translational science · 2021Article
- Potential implications of DMET ontogeny on the disposition of commonly prescribed drugs in neonatal and pediatric intensive care units.Expert opinion on drug metabolism & toxicology · 2021Review
- Cytochrome P450 2A6 is associated with macrophage polarization and is a potential biomarker for hepatocellular carcinoma.FEBS open bio · 2021Article
- Ontogeny of Drug-Metabolizing Enzymes.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Genetic polymorphisms of pharmacogenomic VIP variants in the Dai population from Yunnan province.Molecular genetics & genomic medicine · 2020Article
- Interrogation of CYP2D6 Structural Variant Alleles Improves the Correlation Between CYP2D6 Genotype and CYP2D6-Mediated Metabolic Activity.Clinical and translational science · 2020Article
- How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing?Frontiers in genetics · 2020Review
- Tobacco Smoke Exposure, Urban and Environmental Factors as Respiratory Disease Predictors in Italian Adolescents.International journal of environmental research and public health · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Cytochrome P450 2A6 CYP2A6: metabolizes several clinically relevant substrates, including nicotine, the primary psychoactive component in cigarette smoke. Smokers vary widely in their rate of inactivation and clearance of nicotine, altering numerous smoking phenotypes. We aimed to characterize independent and shared impact of genetic and nongenetic sources of variation in CYP2A6 mRNA, protein, and enzyme activity in a human liver bank (n = 360). For the assessment of genetic factors, we quantified levels of CYP2A6, cytochrome P450 oxidoreductase (POR), and aldo-keto reductase 1D1 (AKR1D1) mRNA, and CYP2A6 and POR proteins. CYP2A6 enzyme activity was determined through measurement of cotinine formation from nicotine and 7-hydroxycoumarin formation from coumarin. Donor DNA was genotyped for CYP2A6, POR, and AKR1D1 genetic variants. Nongenetic factors assessed included gender, age, and liver disease. CYP2A6 phenotype measures were positively correlated to each other (r values ranging from 0.47-0.88, P < 0.001). Female donors exhibited higher CYP2A6 mRNA expression relative to males (P < 0.05). Donor age was weakly positively correlated with CYP2A6 protein (r = 0.12, P < 0.05) and activity (r = 0.20, P < 0.001). CYP2A6 reduced-function genotypes, but not POR or AKR1D1 genotypes, were associated with lower CYP2A6 protein (P < 0.001) and activity (P < 0.01). AKR1D1 mRNA was correlated with CYP2A6 mRNA (r = 0.57, P < 0.001), protein (r = 0.30, P < 0.001), and activity (r = 0.34, P < 0.001). POR protein was correlated with CYP2A6 activity (r = 0.45, P < 0.001). Through regression analyses, we accounted for 17% (P < 0.001), 37% (P < 0.001), and 77% (P < 0.001) of the variation in CYP2A6 mRNA, protein, and activity, respectively. Overall, several independent and shared sources of variation in CYP2A6 activity in vitro have been identified, which could translate to variable hepatic clearance of nicotine.
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