Association of COMT Val108/158Met genotype with smoking cessation in a nicotine replacement therapy randomized trial.
We investigated the association of catechol O-methyltransferase (COMT) genotype with abstinence following a smoking cessation attempt among a large cohort of smokers who attempted to quit using either the nicotine transdermal patch or placebo and were followed up over an 8-year period following their initial cessation attempt. In addition, we examined the possible moderating influence of sex on any association. The genotype x treatment interaction effect at 12-week follow-up indicated a greater benefit of active nicotine replacement treatment compared with placebo on likelihood of abstinence in the COMT Met/Met genotype group (33% versus 12%), in comparison to the Met/Val + Val/Val group (22% versus 16%). Our results indicate that COMT genotype may moderate the effect of active transdermal nicotine patch compared with placebo, with reduced relative benefit of nicotine replacement therapy in individuals with Met/Val or Val/Val genotype. Our data follow an emerging pattern of results suggesting that genetic variation in the dopamine pathway may provide a future basis for tailored smoking cessation therapies, but indicate that different genes influencing various components of this pathway may have different effects on response to smoking cessation pharmacotherapy.
Johnstone
Elaine C
EC
Department of Clinical Pharmacology, University of Oxford, Oxford, United Kingdom.
Elliot
Katherine M
KM
David
Sean P
SP
Murphy
Michael F G
MF
Walton
Robert T
RT
Munafò
Marcus R
MR
D000279:Administration, Cutaneous; D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012737:Sex Factors; D016540:Smoking Cessation; D014029:Tobacco Use Disorder / Q000188:drug therapy*; D016896:Treatment Outcome
D018722:Nicotinic Agonists; D009538:Nicotine; D002394:Catechol O-Methyltransferase