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Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation

The Pharmacogenomics Journal volume 12, pages 86–92 (2012)Cite this article

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Abstract

Smokers (⩾10 cigarettes per day, N=331) of European ancestry taking part in a double-blind placebo-controlled randomized trial of 12 weeks of treatment with bupropion along with counseling for smoking cessation were genotyped for a variable number of tandem repeats polymorphism in exon III of the dopamine D4 receptor gene. Generalized estimating equations predicting point-prevalence abstinence at end of treatment and 2, 6 and 12 months after the end of treatment indicated that bupropion (vs placebo) predicted increased odds of abstinence. The main effect of Genotype was not significant. A Genotype × Treatment interaction (P=0.005) showed that bupropion predicted increased odds of abstinence in long-allele carriers (odds ratios (OR)=1.31, P<0.0001), whereas bupropion was not associated with abstinence among short-allele homozygotes (OR=1.06, P=0.23). The Genotype × Treatment interaction remained when controlling for demographic and clinical covariates (P=0.01) and in analyses predicting continuous abstinence (P's⩽0.054). Bupropion may be more efficacious for smokers who carry the long allele, which is relevant to personalized pharmacogenetic treatment approaches.

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Acknowledgements

This research was supported by NIH grants DA025041 (AML), HL32318 and CA84719 (RN), DA08511 (RAB), DA14276 and DA27331 (SPD) and NIDA-IRP.

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Authors and Affiliations

  1. Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA

    A M Leventhal & M Brightman

  2. Department of Family and Community Medicine, Stanford University School of Medicine, Palo Alto, CA, USA

    S P David

  3. Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA

    D Strong, J E McGeary & R A Brown

  4. Department of Psychology, University of Massachusetts Dartmouth, Dartmouth, MA, USA

    E E Lloyd-Richardson

  5. Department of Experimental Psychology, University of Bristol, Bristol, UK

    M Munafò

  6. Molecular Neurobiology Research Branch, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, USA

    G R Uhl

  7. Schroder Institute, American Legacy Foundation, Washington, DC, USA

    R Niaura

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  1. A M Leventhal
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Correspondence to A M Leventhal.

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Leventhal, A., David, S., Brightman, M. et al. Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation. Pharmacogenomics J 12, 86–92 (2012). https://doi.org/10.1038/tpj.2010.64

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