Objective: To determine the relationship between joint variation in 2 dopaminergic genes and the likelihood of nonsmoking following treatment with bupropion sustained release (SR).

Design: Three hundred twenty-three participants in a bupropion SR smoking cessation effectiveness trial with 12-month follow-up were genotyped for variants of dopamine receptor gene DRD2 and dopamine transporter SLC6A3.

Main outcome measures: Self-reported 7-day point prevalence of nonsmoking.

Results: Neither genotype alone was associated with 7-day point-prevalent nonsmoking at the 12-month follow-up. However, in the presence of the DRD2 A1 allele, SLC6A3 status was significantly associated with the likelihood of nonsmoking at the 12-month follow-up (individuals with DRD2 A1+ and SLC6A3 9- were more likely to be smoking). In the absence of the DRD2 A1 allele, the association between SLC6A3 status and nonsmoking was nonsignificant.

Conclusion: Although these results are suggestive, a more compelling test is needed of the hypothesis that dopaminergic gene interaction underlies, in part, the likelihood of smoking following treatment with bupropion SR. Most likely this will come from larger studies involving prospective randomization to treatment based on genotype.