ArticlePharmacogenetics and genomics2013
A compensatory effect upon splicing results in normal function of the CYP2A6*14 allele.
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 16 papers.
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Who cites it
16 citing papers in PubMed, 16 citations in OpenAlex.
- Phase II trial of S-1 plus leucovorin in patients with advanced gastric cancer and clinical prediction by S-1 pharmacogenetic pathway.Cancer chemotherapy and pharmacology · 2017Trial
- Dual E-Cigarette Users Show Nicotine Addiction Risk Alleles and Nuclear Abnormalities in Oral Epithelial Cells.Advances in respiratory medicine · 2026Article
- Genetic variations in CYP2A6 predict efficacy of neoadjuvant letrozole concurrent with chemotherapy in locally advanced hormone receptor-positive breast cancer.Annals of medicine · 2025Article
- CYP2C19 Plays a Major Role in the HepaticDrug metabolism and disposition: the biological fate of chemicals · 2023Article
- Genetic Variants in Smoking-Related Genes in Two Smoking Cessation Programs: A Cross-Sectional Study.International journal of environmental research and public health · 2021Article
- Pharmacogenetics factors influencing smoking cessation success; the importance of nicotine metabolism.Expert opinion on drug metabolism & toxicology · 2021Review
- A Machine Learning-Based Identification of Genes Affecting the Pharmacokinetics of Tacrolimus Using the DMETInternational journal of molecular sciences · 2020Article
- Nicotine dependence is associated with functional variation in FMO3, an enzyme that metabolizes nicotine in the brain.The pharmacogenomics journal · 2018Article
- CYP2A6 genetic polymorphisms and biomarkers of tobacco smoke constituents in relation to risk of lung cancer in the Singapore Chinese Health Study.Carcinogenesis · 2017Article
- Genetic determinants of cytochrome P450 2A6 activity and biomarkers of tobacco smoke exposure in relation to risk of lung cancer development in the Shanghai cohort study.International journal of cancer · 2016Article
- Genetic determinants of CYP2A6 activity across racial/ethnic groups with different risks of lung cancer and effect on their smoking intensity.Carcinogenesis · 2016Article
- Drug Metabolizing Enzyme and Transporter Gene Variation, Nicotine Metabolism, Prospective Abstinence, and Cigarette Consumption.PloS one · 2015Article
- Novel CYP2A6 variants identified in African Americans are associated with slow nicotine metabolism in vitro and in vivo.Pharmacogenetics and genomics · 2014Article
- Variants in two adjacent genes, EGLN2 and CYP2A6, influence smoking behavior related to disease risk via different mechanisms.Human molecular genetics · 2014Article
- The contribution of common UGT2B10 and CYP2A6 alleles to variation in nicotine glucuronidation among European Americans.Pharmacogenetics and genomics · 2013Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
A synonymous variant in the first exon of CYP2A6, rs1137115 (51G>A), defines the common reference allele CYP2A6*1A, and is associated with lower mRNA expression and slower in-vivo nicotine metabolism. Another common allele, CYP2A6*14, differs from CYP2A6*1A by a single variant, rs28399435 (86G>A, S29N). However, CYP2A6*14 shows in-vivo activity comparable with that of full-function alleles, and significantly higher than CYP2A6*1A. rs1137115A is predicted to create an exonic splicing suppressor site overlapping an exonic splicing enhancer (ESE) site in the first exon of CYP2A6, whereas rs28399435A is predicted to strengthen another adjacent ESE, potentially compensating for rs1137115A. Using an allelic expression assay to assess cDNAs produced from rs1137115 heterozygous liver biopsy samples, lower expression of the CYP2A6*1A allele is confirmed while CYP2A6*14 expression is found to be indistinguishable from that of rs1137115G alleles. Quantitative PCR assays to determine the relative abundance of spliced and unspliced or partially spliced CYP2A6 mRNAs in liver biopsy samples show that *1A/*1A homozygotes have a significantly lower ratio, due to both a reduction in spliced forms and an increase in unspliced or partially spliced CYP2A6. These results show the importance of common genetic variants that effect exonic splicing suppressor and ESEs to explain human variation regarding clinically-relevant phenotypes.
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