Predictors of relapse in a bupropion trial for smoking cessation in recently-abstinent alcoholics: Preliminary results using an aggregate genetic risk score

• Type of Material: Article
• Authors: John E. McGeary, Brown University; Valerie S. Knopik, Brown University; John E. Hayes, Pennsylvania State University; Rohan Palmer, Emory University; Peter M. Monti, Brown University; David Kalman, University of Massachusetts
• Language: English
• Date: 2012-01-01
• Publisher: Libertas Academica
• Publication Version: Final Published Version
• Copyright Statement: © the author(s), publisher and licensee Libertas Academica Ltd.
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.4137/SART.S8866
• Title of Journal or Parent Work: Substance Abuse: Research and Treatment
• ISSN: 1178-2218
• Volume: 6
• Issue: 1
• Start Page: 107
• End Page: 114
• Grant/Funding Information: This work was supported by grants from the National Institute of Drug Abuse at the National Institutes of Health; National Institute on Alcoholism and Alcohol Abuse at the National Institutes of Health; National Center for Research Resources at the National Institutes of Health; and Department of Veteran Affairs, Veterans Health Administration, Office of Research and Development: (grant number R01DA017370 to DK, grant numbers K01DA017671, R01DA023134 to VSK, grant number 5T32AA007459 to JEH and grant number 1S10RR023457, grant number MH019927 to RHP, VA shared equipment grants to JEM).
• Keywords: bupropion; nicotine dependence; pharmacogenetics
• Research Categories: Psychology, Behavioral; Health Sciences, Pharmacology

Abstract

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.