Lastly, the effects of an additional polymorphism in SLC6A3 and cocaine-related behaviors have also been examined. Guindalini et al. (2006) examined the SLC6A3 Intron 8 VNTR (Int8 VNTR), which consists of either five or six repeats and is in moderate to low linkage disequilibrium with the 3′-UTR VNTR (Asherson et al. 2007), and found that the 6-repeat allele was associated with cocaine abuse in a case-control study of cocaine abusers. When the 5- and 6-repeat alleles were cloned into expression vectors and transfected into a dopaminergic cell line, the 6-repeat allele showed increased SLC6A3 expression following treatment with various stimuli (including cocaine), while the 5-repeat allele showed no change in expression. This study, along with Hamidovic et al. (2010a), suggests that polymorphisms other than the 3′-UTR VNTR may also contribute to responses to stimulant drugs.
