In analyses examining associations of amphetamine response with the SLC6A3 3′-UTR VNTR, we found that individuals homozygous for the 9-repeat allele showed decreased responses to amphetamine at 20 mg, compared to heterozygous (9/10) and homozygous (10/10) individuals (Lott et al. 2005). Using a larger sample from the same study, Hamidovic et al. (2010a) tested 4 additional SNPs near the 5′ end of SLC6A3 that were not in linkage disequilibrium with the 3′-UTR VNTR, and found a significant association between the rs460000 C/C genotype and increased scores on the ARCI Euphoria and Stimulation composite scales after 10 and 20 mg amphetamine administration, when compared to A/A and A/C individuals. Interestingly, this SNP is in perfect linkage disequilibrium with rs463379, a SNP that has been associated with increased risk of ADHD (Friedel et al. 2007), which suggests that variants underlying acute response to amphetamine may also underlie disease risk. Overall, these results suggest that both the 3′-UTR VNTR and SNPs in SLC6A3 affect acute response to amphetamine.
