학술논문
Influence of a dopamine pathway additive genetic efficacy score on smoking cessation: results from two randomized clinical trials of bupropion.
Document Type
Academic Journal
Author
David SP; Stanford University School of Medicine, Center for Education and Research in Family and Community Medicine, Division of General Medical Disciplines, Department of Medicine, Stanford, CA, USA; SRI International, Center for Health Sciences, Menlo Park, CA, USA; Alpert Medical School of Brown University, Department of Family Medicine, Pawtucket, RI, USA.; Strong DR; Leventhal AM; Lancaster MA; McGeary JE; Munafò MR; Bergen AW; Swan GE; Benowitz NL; Tyndale RF; Conti DV; Brown RA; Lerman C; Niaura R
Source
Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 9304118 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1360-0443 (Electronic) Linking ISSN: 09652140 NLM ISO Abbreviation: Addiction Subsets: MEDLINE
Subject
Language
English
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, Fagerström Test for Nicotine Dependence, dopamine pathway genotypes (rs1800497 [ANKK1 E713K], rs4680 [COMT V158M], DRD4 exon 3 variable number of tandem repeats polymorphism [DRD4 VNTR], SLC6A3,3' 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 DRD4 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.
(© 2013 Society for the Study of Addiction.)
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, Fagerström Test for Nicotine Dependence, dopamine pathway genotypes (rs1800497 [ANKK1 E713K], rs4680 [COMT V158M], DRD4 exon 3 variable number of tandem repeats polymorphism [DRD4 VNTR], SLC6A3,3' 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 DRD4 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.
(© 2013 Society for the Study of Addiction.)