Abstract
Nicotine is the psychoactive substance responsible for tobacco dependence. It is also a therapeutic used to aid smoking cessation. Cytochrome P450 (CYP)2A6 is the human hepatic enzyme that mediates most of nicotine‘s metabolic inactivation to cotinine. Genetic variation in the CYP2A6 gene can increase or decrease enzyme activity through altering the protein‘s expression level or its structure and function. This article reviews CYP2A6 genetic variation and its impact on in vivo nicotine kinetics, including a description of the individual variants, different phenotyping approaches for assessing in vivo CYP2A6 activity and other sources of variation in nicotine metabolism such as gender. In addition, the effect of CYP2A6 polymorphisms on smoking behavior and tobacco-related lung cancer risk are briefly described. Furthering knowledge in this area will improve interpretation of studies examining smoking behavior, as well as those using nicotine as a therapeutic agent.
Acknowledgements
We thank Nael Al Koudsi, Man Ki Ho, Jibran Khokhar and Eric Siu for their careful revision of this manuscript.
Financial disclosure
Rachel Tyndale holds shares in Nicogen Inc., a company focused on creating novel smoking cessation treatments. No funding for this manuscript was received from Nicogen. This study was supported by the Centre for Addiction and Mental Health, Canadian Institute of Health Research (CIHR) grant MOP53248, Public Health Services Grants DA020830, a Canada Research Chair in Pharmacogenetics, CIHR-Tobacco Use In Special Populations and CIHR-Student Program In Interdisciplinary Capacity Enhancement scholarships. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.