Predictors of relapse in a bupropion trial for smoking cessation in recently-abstinent alcoholics: preliminary results using an aggregate genetic risk score.
- Authors
- McGeary, John E; Knopik, Valerie S; Hayes, John E; Palmer, Rohan H; Monti, Peter M; Kalman, David
- Year
- 2012
- Journal
- Substance abuse : research and treatment
- PMID
- 23032639
- DOI
- 10.4137/SART.S8866
- PMCID
- PMC3460669
INTRODUCTION: Rates of smoking in the US population have decreased overall, but rates in some groups, including alcoholic smokers, remain high. Many newly sober alcoholics are concerned about their smoking and some attempt to quit. However, quit rates in this population are low. Prior studies suggest risk for relapse in this population may be genetically influenced and that genetic factors may moderate response to treatment. METHODS: IN THIS EXPLORATORY STUDY, WE HAD TWO SPECIFIC AIMS: (1) to investigate associations between genetic risk and outcome; (2) to investigate whether genetic risk moderates the efficacy of a medication intervention. Data are from a subsample of 90 participants from a clinical trial of smoking cessation treatment for smokers with between 2 and 12 months of alcohol abstinence. Subjects were randomly assigned to bupropion or placebo. All subjects received counseling and nicotine patches. To examine the possibility that bupropion may have been efficacious in participants with a specific genetic profile (ie, a pharmacogenetic approach), an aggregate genetic risk score was created by combining risk genotypes previously identified in bupropion treatment studies. RESULTS: Although medication efficacy was not moderated by the aggregate genetic risk score, there was an interaction between nicotine dependence and genetic risk in predicting smoking abstinence rates at the end of treatment (10 weeks). CONCLUSIONS: Results suggest an aggregate genetic risk score approach may have utility in treatment trials of alcoholics who smoke. Additionally, these findings suggest a strategy for understanding and interpreting conflicting results for single genetic markers examined as moderators of smoking cessation treatment.
Survival curves based upon median splits of Fagerstrom scores and AGRS used for visual representation of the data.
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|---|---|---|
| 20 | Discussion | other putatively functional variants nearby (e.g.,26). Similarly, variation in the DRD4 gene may be… |
| Name | Type |
|---|---|
| African American | cohort |
| aggregate genetic risk score local | variant |
| AGRS local | phenotype |
| AGRS local | variant |
| AGRS scale local | phenotype |
| alcohol | phenotype |
| alcohol dependence | phenotype |
| alcoholism | phenotype |
| Alcohol Use Disorder | phenotype |
| bupropion | drug |
| bupropion response local | phenotype |
| Cardiac problems local | phenotype |
| cigarettes | phenotype |
| COMT | gene |
| COMT_Val158Met_Met_allele local | variant |
| Condition | phenotype |
| Dependence level local | phenotype |
| DRD2 | gene |
| DRD2 TaqIA | variant |
| DRD2_TaqIA_allele local | variant |
| DRD4 | gene |
| DRD4_exon3_VNTR_≥7_repeats local | variant |
| employment | phenotype |
| epilepsy | phenotype |
| Ethnic ancestry local | phenotype |
| Fagerstrom nicotine dependence local | phenotype |
| Fagerström Test for Nicotine Dependence | phenotype |
| FTND score | phenotype |
| genetic risk | cohort |
| genetic risk score local | phenotype |
| Genetic substudy local | cohort |
| Head injury | phenotype |
| Hispanic/Other local | cohort |
| income | phenotype |
| Main trial local | cohort |
| marital status | phenotype |
| medication condition local | phenotype |
| Medications that lower seizure threshold local | drug |
| mixed European ancestry | cohort |
| nicotine | drug |
| nicotine dependence | phenotype |
| nicotine patch | drug |
| nicotine replacement therapy | drug |
| Occupation local | phenotype |
| pain | phenotype |
| participants | cohort |
| Recently abstinent alcoholics local | cohort |
| relapse | phenotype |
| risk allele | cohort |
| Salivary cotinine local | drug |
| schizophrenia | phenotype |
| sex | phenotype |
| SLC6A3 | gene |
| SLC6A3_9_repeat_allele local | variant |
| Smokers with recent history of alcohol dependence local | cohort |
| smoking | phenotype |
| smoking abstinence | phenotype |
| smoking cessation | phenotype |
| smoking intensity | phenotype |
| smoking phenotypes | phenotype |
| This trial local | cohort |
| time to relapse | phenotype |
| Uncontrolled hypertension local | phenotype |
| Veterans Administration Medical Center participants local | cohort |
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| Systematic Review of Polygenic Gene-Environment Interaction in Tobacco, Alcohol, and Cannabis Use. | Pasman JA et al. | — | 2019 | → |
| From genes to treatments: a systematic review of the pharmacogenetics in smoking cessation. | Salloum NC et al. | — | 2018 | → |
| Leveraging Genomic Data in Smoking Cessation Trials in the Era of Precision Medicine: Why and How. | Chen LS et al. | — | 2018 | → |
| Tobacco use during a clinical trial of mecamylamine for alcohol dependence: Medication effects on smoking and associations with reductions in drinking. | Roberts W et al. | — | 2018 | → |
| Gene-Gene-Environment Interactions of Serotonin Transporter, Monoamine Oxidase A and Childhood Maltreatment Predict Aggressive Behavior in Chinese Adolescents. | Zhang Y et al. | — | 2017 | → |
| Pharmacotherapy for smoking cessation: effects by subgroup defined by genetically informed biomarkers. | Schuit E et al. | — | 2017 | → |
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| Differential sensitivity to the environment: contribution of cognitive biases and genes to psychological wellbeing. | Fox E et al. | — | 2016 | → |
| Genetics moderate alcohol and intimate partner violence treatment outcomes in a randomized controlled trial of hazardous drinking men in batterer intervention programs: A preliminary investigation. | Stuart GL et al. | — | 2016 | → |
| Biomarkers of Response to Smoking Cessation Pharmacotherapies: Progress to Date. | Mamoun M et al. | — | 2015 | → |
| Genetic and Environmental Interplay in Adolescent Substance Use Disorders. | Hines LA et al. | — | 2015 | → |
| Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation. | Chen LS et al. | — | 2015 | → |
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| Antidepressants for smoking cessation. | Hughes JR et al. | — | 2014 | → |
| Genetic associations with intimate partner violence in a sample of hazardous drinking men in batterer intervention programs. | Stuart GL et al. | — | 2014 | → |
| Genetic basis of delay discounting in frequent gamblers: examination of a priori candidates and exploration of a panel of dopamine-related loci. | Gray JC et al. | — | 2014 | → |
| Influence of a dopamine pathway additive genetic efficacy score on smoking cessation: results from two randomized clinical trials of bupropion. | David SP et al. | — | 2013 | → |