ALLELIC ASSOCIATION OF A DOPAMINE TRANSPORTER GENE POLYMORPHISM IN ALCOHOL DEPENDENCE WITH WITHDRAWAL SEIZURES OR DELIRIUM

Hereditary factors confer susceptibility to alcohol dependence, Alcoho l mediates its reinforcing effects by enhancing dopamine activity in t he mesolimbic dopamine system. The role of the dopamine transporter in terminating dopaminergic activity in synaptic neurotransmission sugge sts that variants of the dopamine transporter gene (DAT1) might contri bute to individual differences in vulnerability to addictive behavior. Our population-based association study investigated whether variants of DAT1 confer susceptibility to alcohol dependence in 293 alcoholics and clinically more homogeneous subgroups formed by: positive family h istory, early age-at-onset, delirium, withdrawal seizures, antisocial tendencies, type 1 and 2 alcoholics. Analyzing a VNTR polymorphism in the 3' untranslated region of DAT1, we found a significantly increased prevalence of the nine-repeat allele in 93 alcoholics displaying with drawal seizures or delirium, compared with 93 ethnically matched nonal coholic controls (p = 0.003; OR = 2.44; 95% confidence interval: 1.35- 4.43). Our data provide evidence that a major genetic determinant of D AT1 influences vulnerability to severe alcohol withdrawal symptoms. (C ) 1997 Society of Biological Psychiatry.