ArticlePharmacogenetics and genomics2018
Novel CYP2A6 diplotypes identified through next-generation sequencing are associated with in-vitro and in-vivo nicotine metabolism.
Article in Pharmacogenetics and genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 22 citations in OpenAlex.
- Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer.Nature genetics · 2022Pooled it
- 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
- Precision management of cenobamate in drug-resistant epilepsy: integrating pharmacogenetics, therapeutic drug monitoring, and real-world clinical strategies.Frontiers in pharmacology · 2026Article
- Associating CYP2A6 structural variants with ovarian and lung cancer risk in the UK Biobank: replication and extension.European journal of human genetics : EJHG · 2024Article
- CYP2A6 associates with respiratory disease risk and younger age of diagnosis: a phenome-wide association Mendelian Randomization study.Human molecular genetics · 2024Article
- Quantitative Proteomics in Translational Absorption, Distribution, Metabolism, and Excretion and Precision Medicine.Pharmacological reviews · 2022Review
- Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes.Clinical and translational science · 2022Article
- Nicotine metabolite ratio: Comparison of the three urinary versions to the plasma version and nicotine clearance in three clinical studies.Drug and alcohol dependence · 2021Article
- Analysis of Very Important Pharmacogenomics Variants in the Chinese Lahu Population.Pharmacogenomics and personalized medicine · 2021Article
- Pharmacogenomics of Nicotine Metabolism: Novel CYP2A6 and CYP2B6 Genetic Variation Patterns in Alaska Native and American Indian Populations.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2020Article
- Evaluation of a weighted genetic risk score for the prediction of biomarkers of CYP2A6 activity.Addiction biology · 2020Article
- Cytochrome P450 2A6 whole-gene deletion (CYP2A6*4) polymorphism reduces risk of lung cancer: A meta-analysis.Tobacco induced diseases · 2020Review
- Prevalence of Some Genetic Risk Factors for Nicotine Dependence in Ukraine.Genetics research international · 2019Article
- Preparing the Way: Exploiting Genomic Medicine to Stop Smoking.Trends in molecular medicine · 2018Review
- Variation in CYP2A6 Activity and Personalized Medicine.Journal of personalized medicine · 2017Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
objectivesSmoking patterns and cessation rates vary widely across smokers and can be influenced by variation in rates of nicotine metabolism [i.e. cytochrome P450 2A6 (CYP2A6), enzyme activity]. There is high heritability of CYP2A6-mediated nicotine metabolism (60-80%) owing to known and unidentified genetic variation in the CYP2A6 gene. We aimed to identify and characterize additional genetic variants at the CYP2A6 gene locus.
methodsA new CYP2A6-specific sequencing method was used to investigate genetic variation in CYP2A6. Novel variants were characterized in a White human liver bank that has been extensively phenotyped for CYP2A6. Linkage and haplotype structure for the novel single nucleotide polymorphisms (SNPs) were assessed. The association between novel five-SNP diplotypes and nicotine metabolism rate was investigated.
resultsSeven high-frequency (minor allele frequencies ≥6%) noncoding SNPs were identified as important contributors to CYP2A6 phenotypes in a White human liver bank (rs57837628, rs7260629, rs7259706, rs150298687 (also denoted rs4803381), rs56113850, rs28399453, and rs8192733), accounting for two times more variation in in-vitro CYP2A6 activity relative to the four established functional CYP2A6 variants that are frequently tested in Whites (CYP2A6*2, *4, *9, and *12). Two pairs of novel SNPs were in high linkage disequilibrium, allowing us to establish five-SNP diplotypes that were associated with CYP2A6 enzyme activity (rate of nicotine metabolism) in-vitro in the liver bank and in-vivo among smokers.
conclusionThe novel five-SNP diplotype may be useful to incorporate into CYP2A6 genotype models for personalized prediction of nicotine metabolism rate, cessation success, and response to pharmacotherapies.
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