A dopamine-transporter gene study associated one variant with stronger subjective amphetamine responses. After considering multiple comparisons, the stimulation result was more robust than the euphoria result, and cognitive and cardiovascular associations were not demonstrated.
The exploratory study examined 152 healthy volunteers in a double-blind crossover experiment with placebo and 10- and 20-mg d-amphetamine. Investigators tested four SLC6A3 variants against mood ratings, digit-symbol performance, blood pressure and heart rate. The controlled drug comparison and the observational genotype comparison answer different questions and should remain distinct.
Participants with the rs460000 C/C genotype reported greater stimulation and euphoria than the combined alternative-genotype group. No other responses or tested variants showed significant effects in the reported comparisons. The authors noted that a stringent Bonferroni threshold would preserve the stimulation interaction but not the euphoria finding. It would therefore be misleading to describe every subjective association as equally secure.
The sample was restricted to healthy volunteers of European ancestry, limiting transfer to other populations. A marker can also be linked to nearby variants, so association does not establish which genetic change is biologically responsible. The study did not validate a personal prediction tool for medication response, addiction or impairment. Stronger subjective stimulation is not the same as greater cognitive enhancement or worse driving. Replication, correction for the tested comparisons and prospective predictive performance are needed before practical classification. The useful result is a qualified research association, including the negative physiological and cognitive comparisons.
See genetic attention findings involving a different gene.