J. Gelernter et al., GENETIC ASSOCIATION BETWEEN DOPAMINE TRANSPORTER PROTEIN ALLELES AND COCAINE-INDUCED PARANOIA, Neuropsychopharmacology, 11(3), 1994, pp. 195-200
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.