ArticlePharmacogenetics and genomics2013
Effects upon in-vivo nicotine metabolism reveal functional variation in FMO3 associated with cigarette consumption.
Article in Pharmacogenetics and genomics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Nicotine N-glucuronidation relative to N-oxidation and C-oxidation and UGT2B10 genotype in five ethnic/racial groups.Carcinogenesis · 2014Trial
- Biochemical and genetic biomarkers associated with nicotine dependence in Mexican smokers.Pharmacology research & perspectives · 2023Article
- Estimation of FMO3 Ontogeny by Mechanistic Population Pharmacokinetic Modelling of Risdiplam and Its Impact on Drug-Drug Interactions in Children.Clinical pharmacokinetics · 2023Article
- Impact of Genetic Variants in the Nicotine Metabolism Pathway on Nicotine Metabolite Levels in Smokers.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2023Article
- Roles of selected non-P450 human oxidoreductase enzymes in protective and toxic effects of chemicals: review and compilation of reactions.Archives of toxicology · 2022Review
- Pharmacogenetics factors influencing smoking cessation success; the importance of nicotine metabolism.Expert opinion on drug metabolism & toxicology · 2021Review
- Arecoline N-oxide regulates oral squamous cell carcinoma development through NOTCH1 and FAT1 expressions.Journal of cellular physiology · 2019Article
- Nicotine-Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2019Article
- Biosignature Discovery for Substance Use Disorders Using Statistical Learning.Trends in molecular medicine · 2018Review
- Nicotine dependence is associated with functional variation in FMO3, an enzyme that metabolizes nicotine in the brain.The pharmacogenomics journal · 2018Article
- Genetic and Nongenetic Factors Associated with Protein Abundance of Flavin-Containing Monooxygenase 3 in Human Liver.The Journal of pharmacology and experimental therapeutics · 2017Article
- Effect of UGT2B10, UGT2B17, FMO3, and OCT2 genetic variation on nicotine and cotinine pharmacokinetics and smoking in African Americans.Pharmacogenetics and genomics · 2017Article
- Targeted sequencing identifies genetic polymorphisms of flavin-containing monooxygenase genes contributing to susceptibility of nicotine dependence in European American and African American.Brain and behavior · 2017Article
- Article
- Drug Metabolizing Enzyme and Transporter Gene Variation, Nicotine Metabolism, Prospective Abstinence, and Cigarette Consumption.PloS one · 2015Article
- Variation in P450 oxidoreductase (POR) A503V and flavin-containing monooxygenase (FMO)-3 E158K is associated with minor alterations in nicotine metabolism, but does not alter cigarette consumption.Pharmacogenetics and genomics · 2014Article
- The contribution of common UGT2B10 and CYP2A6 alleles to variation in nicotine glucuronidation among European Americans.Pharmacogenetics and genomics · 2013Article
- Biochemistry of nicotine metabolism and its relevance to lung cancer.The Journal of biological chemistryReview
- Metabolite Profiling of Clozapine in Patients Switching Versus Maintaining Treatment: A Retrospective Pilot Study.Journal of clinical psychopharmacologyArticle
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundFlavin-containing monooxygenases (FMO) catalyze the metabolism of nucleophilic heteroatom-containing drugs and xenobiotics, including nicotine. Rare mutations in FMO3 are responsible for defective N-oxidation of dietary trimethylamine leading to trimethylaminuria, and common genetic variation in FMO3 has been linked to interindividual variability in metabolic function that may be substrate specific.
methodsA genetic model of CYP2A6 function is used as a covariate to reveal functional polymorphism in FMO3 that indirectly influences the ratio of deuterated nicotine metabolized to cotinine following oral administration. The association is tested between FMO3 haplotype and cigarette consumption in a set of nicotine-dependent smokers.
resultsFMO3 haplotype, based on all common coding variants in Europeans, significantly predicts nicotine metabolism and accounts for ∼2% of variance in the apparent percent of nicotine metabolized to cotinine. The metabolic ratio is not associated with FMO2 haplotype or an FMO1 expression quantitative trait locus. Cross-validation demonstrates calculated FMO3 haplotype parameters to be robust and significantly improve the predictive nicotine metabolism model over CYP2A6 genotype alone. Functional classes of FMO3 haplotypes, as determined by their influence on nicotine metabolism to cotinine, are also significantly associated with cigarettes per day in nicotine-dependent European Americans (n=1025, P=0.04), and significantly interact (P=0.016) with CYP2A6 genotype to predict cigarettes per day.
conclusionThese findings suggest that common polymorphisms in FMO3 influence nicotine clearance and that these genetic variants in turn influence cigarette consumption.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.