Polymorphisms in Dopamine Transporter (SLC6A3) are Associated with Stimulant Effects of d-Amphetamine: An Exploratory Pharmacogenetic Study Using Healthy Volunteers
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- Hamidovic, A., Dlugos, A., Palmer, A.A. et al. Behav Genet (2010) 40: 255. doi:10.1007/s10519-009-9331-7
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Individuals vary in their subjective responses to stimulant drugs, and these differences are believed to be partially genetic in origin. We evaluated associations between mood, cognitive and cardiovascular responses to d-amphetamine and four polymorphisms in the dopamine transporter (SLC6A3): rs460000, rs3756450, rs37022 and rs6869645. Healthy Caucasian male and female volunteers (N = 152) participated in a double-blind, crossover design study in which they received placebo, 10 and 20 mg of d-amphetamine. We measured self-reported rating of mood, performance on the Digit Symbol Substitution Task, blood pressure and heart rate. Individuals with the C/C genotype at rs460000 (N = 83) reported approximately twofold higher ratings of stimulation and euphoria relative to the A/A+A/C (N = 69) genotype group, at both the 10 and 20 mg doses. No other responses or SNPs showed significant effects. rs460000 is in perfect LD with rs463379 (CEU: D′ = 1; r2 = 1), which was not studied here, but has been associated with etiology of Attention Deficit Hyperactivity Disorder (ADHD). These findings suggest a pleiotropic effect of this polymorphic locus on both ADHD and sensitivity to the subjective effects of amphetamine.