Genetic association between dopamine transporter protein alleles and cocaine-induced paranoia.
Paranoia in the context of cocaine abuse is common and potentially dangerous. 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 protein (DAT1) contains a variable number of tandem repeats (VNTR) polymorphism 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, it is close to the coding region and could plausibly be in linkage disequilibrium with a mutation in the gene. Cocaine blocks the dopamine transporter and increases synaptic availability of dopamine. We examined DAT alleles in 58 white and 45 black cocaine users in order to test only two hypotheses: (1) Is there an allelic association between DAT and cocaine dependence? and (2) Is there an allelic association between DAT and cocaine-induced paranoia? We did not demonstrate an allelic association with cocaine dependence. However, within the white sample, DAT genotype was associated with cocaine-induced paranoia (allele frequency for allele 9 = .16 for those without 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 measure in the black sample. Certain DAT genotypes may therefore predispose to paranoia in the context of cocaine use in white populations. We caution that these results require independent replication.
Gelernter
J
J
Department of Psychiatry, Yale University School of Medicine, West Haven, Connecticut.
Kranzler
H R
HR
Satel
S L
SL
Rao
P A
PA
D000328:Adult; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D003042:Cocaine / Q000009:adverse effects*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010259:Paranoid Disorders / Q000139:chemically induced* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D019966:Substance-Related Disorders / Q000235:genetics
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; D003042:Cocaine