Influence of a dopamine pathway additive genetic efficacy score on smoking cessation: results from two randomized clinical trials of bupropion
Year: 2013
Type: article
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.
Source: Addiction
DOI: 10.1111/add.12325
Institutions: SRI International, Brown University, Stanford Medicine, Stanford University, University of California San Diego, University of Southern California, Providence VA Medical Center, University of Bristol, University of California, San Francisco, Centre for Addiction and Mental Health, University of Toronto, University of Pennsylvania, Truth Initiative, Johns Hopkins University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1028571699, G109268784, G1093052639, Transdisciplinary Tobacco Use Research Centers, Exploratory/Developmental Study of Pharmacogenetic Smoking Cessation Therapy, G1811213690, G2151022117, The PharmGKB: Catalyzing Research in Pharmacogenetics, G3144795810, PharmGKB: pharmacogenomics knowledge for precision medicine, CHEMOTHERAPY FOR IMMUNE DESTRUCTION OF EBV TUMORS, G3885305622, Southern California Clinical and Translational Science Institute, G5046995802, G5094963604, Psychobiological /Genetic Determinants-Smoking Cessation, Nicotine Dependence: Phenotype, Endophenotype & Contexts, DMET Genes, Nicotine Metabolism and Prospective Abstinence, MATCHING ANTIDEPRESSANT TREATMENT FOR SMOKING CESSATION, Affective and Genetic Correlates of Amphetamine Response, Extended Treatment for Smoking Cessation, Pharmacogenetics of Nicotine Addiction Treatment, G7382922652, Abramson Cancer Center Support Grant
OpenAlex ID: W1607776125