GENETIC ASSOCIATION BETWEEN DOPAMINE TRANSPORTER PROTEIN ALLELES AND COCAINE-INDUCED PARANOIA

Paranoia in the context of cocaine abuse is common and potentially dan gerous. Several lines of evidence suggest that this phenomenon may be related to function of the dopamine transporter protein (DAT). DAT is the site of presynaptic reuptake of dopamine, an event that terminates its synaptic activity. The gene coding for dopamine transporter prote in (DAT1) contains a variable number of tandem repeats (VNTR) polymorp hism in the 3' untranslated region that can be typed by the polymerase chain reaction (PCR) (Vandenbergh et al. 1992). Although this is not a coding region polymorphism if is close to the coding region and coul d plausibly be in linkage disequilibrium with a mutation in the gene. Cocaine blacks the dopamine transporter and increases synaptic availab ility of dopamine. We examined DAT alleles in 58 white and 45 black co caine users in order to test only two hypotheses: (1) Is there an alle lic association between DAT and cocaine dependence? and (2) Is there a n allelic association between DAT and cocaine-induced paranoia? We did not demonstrate an allelic association with cocaine dependence. Howev er, within the white sample, DAT genotype was associated with cocaine- induced paranoia (allele frequency for allele 9 = .16 for those withou t paranoid experiences versus .35 for those with, chi(2) = 3.9 [2 x 2 table], p < .05). There was no significant difference for the same mea sure in the black sample. Certain DAT genotypes may therefore predispo se to paranoia in the context of cocaine use in white populations. We caution that these results require independent replication.