1. ¹Department of Psychiatry and Abramson Cancer Center, Tobacco Use Research Center, University of Pennsylvania, Philadelphia, PA, USA
2. ²Department of Pediatrics, State University of New York (SUNY) Buffalo, Buffalo, NY, USA
3. ³Molecular Diagnosis and Genotyping Facility, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
4. ⁴Department of Psychology, State University of New York (SUNY) at Buffalo, Buffalo, NY, USA
5. ⁵Department of Psychiatry & Human Behavior, Transdisciplinary Research, Butler Hospital, Providence, RI, USA
6. ⁶Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, PA, USA

Correspondence: Dr C Lerman, Department of Psychiatry and Abramson Cancer Center, Tobacco Use Research Center, University of Pennsylvania, 3535 Market Street, Suite 4100, Philadelphia, PA 19104, USA. Tel: +1 215 746 7141; Fax: +1 215 746 7140; E-mail: clerman@mail.med.upenn.edu

Received 12 November 2004; Revised 9 June 2005; Accepted 27 June 2005; Published online 10 August 2005.

Abstract

Although bupropion and nicotine replacement therapy (NRT) are efficacious tobacco dependence treatments, there is substantial interindividual variability in therapeutic response and most smokers relapse. Pharmacogenetics research may improve treatment outcomes by identifying genetic variants predictive of therapeutic response. We investigated the roles of two functional genetic variants in the dopamine D2 receptor (DRD2) gene in response to pharmacotherapy for tobacco dependence among participants in two randomized clinical trials with a 6-month follow-up period: a double-blind placebo-controlled trial of bupropion (n=414) and an open label trial of transdermal nicotine vs nicotine nasal spray (n=368). At the end of the treatment phase, a statistically significant (p=0.01) interaction between the DRD2 - 141C Ins/Del genotype and treatment indicated a more favorable response to bupropion among smokers homozygous for the Ins C allele compared to those carrying a Del C allele. By contrast, smokers carrying the Del C allele had statistically significantly (p=0.006) higher quit rates on NRT compared to those homozygous for the Ins C allele, independent of NRT type. The C957T variant was also associated (p=0.03) with abstinence following NRT. These results suggest that bupropion may be the preferred pharmacologic treatment for smokers homozygous for the DRD2 - 141 Ins C allele, while NRT may be more beneficial for those who carry the Del C allele. Study findings require confirmation in additional larger samples before they are applied in practice.