These authors contributed equally to this study
Pharmacotherapy effects on smoking cessation vary with nicotine metabolism gene (CYP2A6)
Article first published online: 11 NOV 2013
© 2013 Society for the Study of Addiction
Volume 109, Issue 1, pages 128–137, January 2014
How to Cite
Chen, L.-S., Bloom, A. J., Baker, T. B., Smith, S. S., Piper, M. E., Martinez, M., Saccone, N., Hatsukami, D., Goate, A. and Bierut, L. (2014), Pharmacotherapy effects on smoking cessation vary with nicotine metabolism gene (CYP2A6). Addiction, 109: 128–137. doi: 10.1111/add.12353
- Issue published online: 12 DEC 2013
- Article first published online: 11 NOV 2013
- Accepted manuscript online: 11 SEP 2013 05:43AM EST
- Manuscript Accepted: 3 SEP 2013
- Manuscript Revised: 27 JUN 2013
- Manuscript Received: 25 APR 2013
- NIH. Grant Numbers: P01 CA089392, P50 CA84724
- National Cancer Institute. Grant Number: K05CA139871
- National Institute on Drug Abuse. Grant Numbers: P50 DA19706, R01 DA026911, K02 DA021237, K08 DA030398
- National Human Genome Research Institute. Grant Number: U01 HG004422
- National Center for Research Resources. Grant Number: KL2 RR024994
- National Institute of Mental Health. Grant Number: 5T32MH014677-33
- Wisconsin Partnership Program
- smoking cessation
Background and aims
Evidence suggests that both the nicotinic receptor α5 subunit (CHRNA5) and Cytochrome P450 2A6 (CYP2A6) genotypes influence smoking cessation success and response to pharmacotherapy. We examine the effect of CYP2A6 genotype on smoking cessation success and response to cessation pharmacotherapy, and combine these effects with those of CHRNA5 genotypes.
Placebo-controlled randomized smoking cessation trial.
Ambulatory care facility in Wisconsin, USA.
Smokers (n = 709) of European ancestry were randomized to placebo, bupropion, nicotine replacement therapy or combined bupropion and nicotine replacement therapy.
Survival analysis was used to model time to relapse using nicotine metabolism derived from CYP2A6 genotype-based estimates. Slow metabolism is defined as the lowest quartile of estimated metabolic function.
CYP2A6-defined nicotine metabolic function moderated the effect of smoking cessation pharmacotherapy on smoking relapse over 90 days [hazard ratio (HR) = 2.81, 95% confidence interval (CI) = 1.32–5.99, P = 0.0075], with pharmacotherapy significantly slowing relapse in fast (HR = 0.39, 95% CI = 0.28–0.55, P = 1.97 × 10−8), but not slow metabolizers (HR = 1.09, 95% CI = 0.55–2.17, P = 0.80). Further, only the effect of nicotine replacement, and not bupropion, varies with CYP2A6-defined metabolic function. The effect of nicotine replacement on continuous abstinence is moderated by the combined genetic risks from CYP2A6 and CHRNA5 (Wald = 7.44, d.f. = 1, P = 0.0064).
Nicotine replacement therapy is effective among individuals with fast, but not slow, CYP2A6-defined nicotine metabolism. The effect of bupropion on relapse likelihood is unlikely to be affected by nicotine metabolism as estimated from CYP2A6 genotype. The variation in treatment responses among smokers with genes may guide future personalized smoking cessation interventions.