Influence of a dopamine pathway additive genetic efficacy score on smoking cessation: results from two randomized clinical trials of bupropion. (18th September 2013)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Addiction. Volume 108:Number 12(2013:Dec.)
• Page Start: 2202
• Page End: 2211
• Publication Date: 2013-09-18
• Subjects: Alcoholism -- Periodicals; Drug addiction -- Periodicals; 616.86
• DOI: 10.1111/add.12325
• Languages: English
• ISSNs: 0965-2140

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="add12325-sec-0001" sec-type="section"> <title>Aims</title> <p>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.</p> </sec> <sec id="add12325-sec-0002" sec-type="section"> <title>Design</title> <p>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.</p> </sec> <sec id="add12325-sec-0003" sec-type="section"> <title>Setting</title> <p>Two hospital‐affiliated clinics (study 1), and two university‐affiliated clinics (study 2).</p> </sec> <sec id="add12325-sec-0004" sec-type="section"> <title>Participants</title> <p>A total of 792 self‐identified white treatment‐seeking smokers aged ≥18 years smoking ≥10 cigarettes per day over the last year.</p> </sec> <sec id="add12325-sec-0005" sec-type="section"> <title>Measurements</title> <p>Age, gender, Fagerström Test for Nicotine Dependence, dopamine pathway genotypes (rs1800497 <italic>[ANKK1</italic> E713K], rs4680 [<italic>COMT</italic> V158M], <italic>DRD4</italic> exon 3 variable number of tandem repeats polymorphism [<italic>DRD4</italic> VNTR], <italic>SLC6A3, 3′</italic> VNTR) analyzed both separately and as part of an AGES, time to first lapse and point prevalence abstinence at end of treatment.</p> </sec> <sec id="add12325-sec-0006" sec-type="section"> <title>Findings</title> <p>Significant associations of the AGES (hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.06–1.14, <italic>P</italic> = 0.009) and of the <italic>DRD4</italic> VNTR (HR = 1.29, 95% CI = 1.17–1.41, <italic>P</italic> = 0.0073) were observed with time to first lapse. A significant AGES by pharmacotherapy interaction was observed (β standard error = −0.18 [0.07], <italic>P</italic> = 0.016), such that AGES predicted risk for time to first lapse only for individuals randomized to placebo.</p> </sec> <sec id="add12325-sec-0007" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>