OBJECTIVES: To examine the association between polymorphisms in the dopamine transporter gene (SLC6A3, DAT1) and treatment outcome in smokers attempting to quit using either nicotine replacement therapy or bupropion. METHODS: The sample consisted of 583 smokers recruited from a smoking cessation clinic, and followed throughout the 4 weeks of post-cessation treatment with behavioural support and either nicotine replacement therapy or bupropion. RESULTS: At 1 week after smoking cessation, the 3' untranslated region (3'UTR) variable number of tandem repeats (VNTRs) and the 30-bp intron 8 VNTR DAT1 genotypes were associated with the ability to stop smoking (3'UTR VNTR, odds ratio=2.0, 95% confidence interval=1.2-3.5, novel intron 8 VNTR, odds ratio=1.8, 95% confidence interval=1.0-2.9), controlling for potential confounders. The results were weaker and no longer significant at a 4-week follow-up. CONCLUSIONS: We find evidence, although modest, of a medium-sized effect of DAT1 genotype on the ability to stop smoking early in a smoking cessation attempt. If the effect is real, and is strongest in the very early stages of smoking cessation, this suggests that the primary utility of DAT1 screening in this field will be in the identification of those most at risk of early relapse after quitting.
OBJECTIVES: To examine the association between polymorphisms in the dopamine transporter gene (SLC6A3, DAT1) and treatment outcome in smokers attempting to quit using either nicotine replacement therapy or bupropion. METHODS: The sample consisted of 583 smokers recruited from a smoking cessation clinic, and followed throughout the 4 weeks of post-cessation treatment with behavioural support and either nicotine replacement therapy or bupropion. RESULTS: At 1 week after smoking cessation, the 3' untranslated region (3'UTR) variable number of tandem repeats (VNTRs) and the 30-bp intron 8 VNTR DAT1 genotypes were associated with the ability to stop smoking (3'UTR VNTR, odds ratio=2.0, 95% confidence interval=1.2-3.5, novel intron 8 VNTR, odds ratio=1.8, 95% confidence interval=1.0-2.9), controlling for potential confounders. The results were weaker and no longer significant at a 4-week follow-up. CONCLUSIONS: We find evidence, although modest, of a medium-sized effect of DAT1 genotype on the ability to stop smoking early in a smoking cessation attempt. If the effect is real, and is strongest in the very early stages of smoking cessation, this suggests that the primary utility of DAT1 screening in this field will be in the identification of those most at risk of early relapse after quitting.
Authors: Richard C McEachin; Nancy L Saccone; Scott F Saccone; Yelena D Kleyman-Smith; Tiara Kar; Rajesh K Kare; Alex S Ade; Maureen A Sartor; James D Cavalcoli; Melvin G McInnis Journal: BMC Med Genet Date: 2010-01-26 Impact factor: 2.103