title: Association of COMT Val108/158Met genotype with smoking cessation in a nicotine replacement therapy randomized trial.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, University of Oxford, Oxford, United Kingdom.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Johnstone
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Elliot
authors.forename: Sean P
authors.initials: SP
authors.lastname: David
authors.forename: Michael F G
authors.initials: MF
authors.lastname: Murphy
authors.forename: Robert T
authors.initials: RT
authors.lastname: Walton
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Munafò
mesh_terms: 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
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine; D002394:Catechol O-Methyltransferase