ArticlePharmacogenetics and genomics2013
The contribution of common UGT2B10 and CYP2A6 alleles to variation in nicotine glucuronidation among European Americans.
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 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Genome-Wide Meta-Analysis of Cotinine Levels in Cigarette Smokers Identifies Locus at 4q13.2.Scientific reports · 2016Pooled it
- 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
- Effects of Genetic Variants in the Nicotine Metabolism Pathway on Smoking Cessation.Genetics research · 2022Article
- Pharmacogenetics factors influencing smoking cessation success; the importance of nicotine metabolism.Expert opinion on drug metabolism & toxicology · 2021Review
- Genetic variants in CYP2A6 and UGT1A9 genes associated with urinary nicotine metabolites in young Mexican smokers.The pharmacogenomics journal · 2020Article
- 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
- Effect of UGT2B10, UGT2B17, FMO3, and OCT2 genetic variation on nicotine and cotinine pharmacokinetics and smoking in African Americans.Pharmacogenetics and genomics · 2017Article
- Nicotine Metabolism and Smoking: Ethnic Differences in the Role of P450 2A6.Chemical research in toxicology · 2017Article
- The contribution of common genetic variation to nicotine and cotinine glucuronidation in multiple ethnic/racial populations.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundTo develop a predictive genetic model of nicotine metabolism. UDP-glucuronosyltransferase-2B10 (UGT2B10) is the primary catalyst of nicotine glucuronidation. MATERIALS AND
methodsThe conversion of deuterated (D2)-nicotine to D2-nicotine-glucuronide, D2-cotinine, D2-cotinine-glucuronide, and D2-trans-3'-hydroxycotinine were quantified in 188 European Americans, and the contribution of UGT2B10 genotype to variability in first-pass nicotine glucuronidation assessed, following a procedure previously applied to nicotine C-oxidation. The proportion of total nicotine converted to nicotine-glucuronide [D2-nicotine-glucuronide/(D2-nicotine+D2-nicotine-glucuronide+D2-cotinine+D2-cotinine-glucuronide+D2-trans-3'-hydroxycotinine)] was the primary phenotype.
resultsThe variant, rs61750900T (D67Y) (minor allele frequency=10%), is confirmed to abolish nicotine glucuronidation activity. Another variant, rs112561475G (N397D) (minor allele frequency=2%), is significantly associated with enhanced glucuronidation. rs112561475G is the ancestral allele of a well-conserved amino acid, indicating that the majority of human UGT2B10 alleles are derived hypomorphic alleles.
conclusionCYP2A6 and UGT2B10 genotype explain 53% of the variance in oral nicotine glucuronidation in this sample. CYP2A6 and UGT2B10 genetic variants are also significantly associated with undeuterated (D0) nicotine glucuronidation in individuals smoking ad libitum. We find no evidence for further common variation markedly influencing hepatic UGT2B10 expression in European Americans.
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