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Influence of a dopamine pathway additive genetic efficacy score on smoking cessation: results from two randomized clinical trials of bupropion
Author(s) -
David Sean P.,
Strong David R.,
Leventhal Adam M.,
Lancaster Molly A.,
McGeary John E.,
Munafò Marcus R.,
Bergen Andrew W.,
Swan Gary E.,
Benowitz Neal L.,
Tyndale Rachel F.,
Conti David V.,
Brown Richard A.,
Lerman Caryn,
Niaura Raymond
Publication year - 2013
Publication title -
addiction
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.424
H-Index - 193
eISSN - 1360-0443
pISSN - 0965-2140
DOI - 10.1111/add.12325
Subject(s) - medicine , bupropion , smoking cessation , rs4680 , randomized controlled trial , abstinence , nicotine patch , varenicline , confidence interval , nicotine , placebo , physical therapy , psychiatry , catechol o methyl transferase , allele , biochemistry , chemistry , alternative medicine , pathology , gene
Abstract Aims To evaluate the associations of treatment and an additive genetic efficacy score ( AGES ) based on dopamine functional polymorphisms with time to first smoking lapse and point prevalence abstinence at end of treatment among participants enrolled into two randomized clinical trials of smoking cessation therapies. Design Double‐blind pharmacogenetic efficacy trials randomizing participants to active or placebo bupropion. Study 1 also randomized participants to cognitive–behavioral smoking cessation treatment ( CBT ) or this treatment with CBT for depression. Study 2 provided standardized behavioural support. Setting Two hospital‐affiliated clinics (study 1), and two university‐affiliated clinics (study 2). Participants A total of 792 self‐identified white treatment‐seeking smokers aged ≥18 years smoking ≥10 cigarettes per day over the last year. Measurements Age, gender, F agerström T est for N icotine D ependence, dopamine pathway genotypes (rs1800497 [ ANKK 1 E 713 K ], rs4680 [ COMT V 158 M ], DRD 4 exon 3 variable number of tandem repeats polymorphism [ DRD 4 VNTR ], SLC 6 A 3,3′ VNTR ) analyzed both separately and as part of an AGES , time to first lapse and point prevalence abstinence at end of treatment. Findings Significant associations of the AGES (hazard ratio [HR] = 1.10, 95% confidence interval [ CI ] = 1.06–1.14, P = 0.009) and of the DRD 4 VNTR ( HR = 1.29, 95% CI = 1.17–1.41, P = 0.0073) were observed with time to first lapse. A significant AGES by pharmacotherapy interaction was observed (β standard error = −0.18 [0.07], P = 0.016), such that AGES predicted risk for time to first lapse only for individuals randomized to placebo. Conclusions A score based on functional polymorphisms relating to dopamine pathways appears to predict lapse to smoking following a quit attempt, and the association is mitigated in smokers using bupropion.