ArticlePharmacogenetics and genomics2008
A novel CYP2A6 allele, CYP2A6*23, impairs enzyme function in vitro and in vivo and decreases smoking in a population of Black-African descent.
Article in Pharmacogenetics and genomics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- Nicotine Metabolism Predicted by CYP2A6 Genotypes in Relation to Smoking Cessation: A Systematic Review.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2022Pooled it
- Systematic review of the relationship between the 3-hydroxycotinine/cotinine ratio and cigarette dependence.Psychopharmacology · 2011Pooled it
- Assessment of Racial Differences in Pharmacotherapy Efficacy for Smoking Cessation: Secondary Analysis of the EAGLES Randomized Clinical Trial.JAMA network open · 2021Trial
- A clinical trial to examine disparities in quitting between African-American and White adult smokers: Design, accrual, and baseline characteristics.Contemporary clinical trials · 2016Trial
- Plasma letrozole concentrations in postmenopausal women with breast cancer are associated with CYP2A6 genetic variants, body mass index, and age.Clinical pharmacology and therapeutics · 2011Trial
- A pilot clinical trial of varenicline for smoking cessation in black smokers.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2011Trial
- Association of nicotine metabolite ratio and CYP2A6 genotype with smoking cessation treatment in African-American light smokers.Clinical pharmacology and therapeutics · 2009Trial
- Natural Polymorphic Variants in the CYP450 Superfamily: A Review of Potential Structural Mechanisms and Functional Consequences.International journal of molecular sciences · 2025Review
- Fine-mapping the CYP2A6 regional association with nicotine metabolism among African American smokers.Molecular psychiatry · 2025Article
- PharmVar GeneFocus: CYP2A6.Clinical pharmacology and therapeutics · 2024Review
- Human Cytochrome P450 1, 2, 3 Families as Pharmacogenes with Emphases on Their Antimalarial and Antituberculosis Drugs and Prevalent African Alleles.International journal of molecular sciences · 2023Review
- Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes.Clinical and translational science · 2022Article
- Transferability of Ancestry-Specific and Cross-Ancestry CYP2A6 Activity Genetic Risk Scores in African and European Populations.Clinical pharmacology and therapeutics · 2021Article
- Pharmacogenetics factors influencing smoking cessation success; the importance of nicotine metabolism.Expert opinion on drug metabolism & toxicology · 2021Review
- Pregnant Smokers Receiving Opioid Agonist Therapy Have an Elevated Nicotine Metabolite Ratio: A Replication Study.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2020Article
- Factors That Explain Differences in Abstinence Between Black and White Smokers: A Prospective Intervention Study.Journal of the National Cancer Institute · 2019Article
- Genome-wide association study of a nicotine metabolism biomarker in African American smokers: impact of chromosome 19 genetic influences.Addiction (Abingdon, England) · 2018Article
- Variation in CYP2A6 Activity and Personalized Medicine.Journal of personalized medicine · 2017Review
- Metronidazole Metabolism in Neonates and the Interplay Between Ontogeny and Genetic Variation.Journal of clinical pharmacology · 2017Article
- Distribution of polymorphic variants of CYP2A6 and their involvement in nicotine addiction.EXCLI journal · 2017Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesCYP2A6 is the main enzyme involved in nicotine metabolism in humans. We have identified a novel allele, CYP2A6*23 (2161C>T, R203C), in individuals of Black-African descent and investigated its impact on enzyme activity and association with smoking status.
methodsWild-type and variant enzymes containing amino acid changes R203C (CYP2A6*23), R203S (CYP2A6*16) and V365M (CYP2A6*17) were expressed in Escherichia coli. The effect of CYP2A6*23 in vivo was examined in individuals of Black-African descent given 4 mg oral nicotine.
resultsCYP2A6*23 occurred at an allele frequency of 2.0% in individuals of Black-African descent (N=560 alleles, 95% confidence interval, 0.8-3.1%) and was not detected in Caucasians (N=334 alleles), Chinese (N=288 alleles) or Japanese (N=104 alleles). In vitro, CYP2A6.23 had greatly reduced activity toward nicotine C-oxidation similar to CYP2A6.17, as well as reduced coumarin 7-hydroxylation. Conversely, CYP2A6.16 did not differ in activity compared with the wild-type enzyme. The trans-3'-hydroxycotinine to cotinine ratio, a phenotypic measure of CYP2A6 activity in vivo, was lower in CYP2A6*1/*23 and CYP2A6*23/*23 individuals (mean adjusted ratio of 0.60, n=5) compared with CYP2A6*1/*1 individuals (mean adjusted ratio of 1.21, n=150) (P<0.04). CYP2A6*23 trended toward a higher allele frequency in nonsmokers (3.1%, N=9/286 alleles) compared with smokers (0.7%, N=2/274 alleles) (P=0.06).
conclusionThese results suggest the novel CYP2A6*23 allele impairs enzyme function in vitro and in vivo and trends toward an association with lower risk of smoking.
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What OpenQuestion holds
Registered trials
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.