Pharmacogenetics factors influencing smoking cessation success; the importance of nicotine metabolism

ABSTRACT

Introduction: Smoking remains a worldwide epidemic, and despite an increase in public acceptance of the harms of tobacco use, it remains the leading cause of preventable death. It is estimated that up to 70% of all smokers express a desire to quit, but only 3–5% of them are successful.

Areas covered: The goal of this review was to evaluate the current status of smoking cessation treatments and the feasibility of implementing personalized-medicine approaches to these pharmacotherapies. We evaluated the genetics associated with higher levels of nicotine addiction and follow with an analysis of the genetic variants that affect the nicotine metabolic ratio (NMR) and the FDA approved treatments for smoking cessation. We also highlighted the gaps in the process of translating current laboratory understanding into clinical practice, and the benefits of personalized treatment approaches for a successful smoking cessation strategy.

Expert opinion: Evidence supports the use of tailored therapies to ensure that the most efficient treatments are utilized in an individual’s smoking cessation efforts. An understanding of the genetic effects on the efficacy of individualized smoking cessation pharmacotherapies is key to smoking cessation, ideally utilizing a polygenetic risk score that considers all genetic variation.

KEYWORDS:

• Nicotine
• metabolism
• cytochrome P450
• udp glucuronosyltransferase
• flavin monooxygenase
• nicotine metabolism ratio
• bupropion
• varenicline
• nicotine replacement therapy
• tobacco cessation
• pharmacogenetics

Article highlights

• Smoking is the leading preventable cause of death; although 70% of smokers desire to quit only 3-5% are successful.

• Genetic variation in nicotine acetylcholine receptors results in differences in addiction to nicotine between individuals.

• The metabolism of nicotine varies greatly between individuals due to genetic variation in these pathways, leading to unique nicotine clearance rates, and as a consequence results in varying levels of nicotine exposure between individuals.

• Smoking cessation pharmacotherapies (nicotine replacement therapy, varenicline, and bupropion) are metabolized differently among individuals, suggesting that personalized approaches to maximize smoking cessation outcomes are warranted.

More research is needed to achieve personalized smoking cessation approaches to improve smoking cessation outcomes. A polygenic risk score that incorporates all sources of variation in nicotine metabolism and target pathways is necessary to increase smoking cessation success.

This box summarizes key points contained in the article.

Acknowledgments

The authors thank Gang Chen, PhD and Christy J.W. Watson, M.S. of Washington State University for their careful reading and advice to prepare this manuscript.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded in part by the National Institutes of Health, National Institutes of Environmental Health Sciences (grant R01ES025460 to P. Lazarus) and from the Health Sciences and Services Authority of Spokane, WA to WSU College of Pharmacy and Pharmaceutical Sciences (grant WSU002292). This paper was also funded in part by the Fulbright-Garcia Robles Program and a CONACyT dissertation grant to Y.X. Perez-Paramo.