Allelic association of a dopamine transporter gene polymorphism in alcohol dependence with withdrawal seizures or delirium

Hereditary factors confer susceptibility to alcohol dependence. Alcohol mediates its reinforcing effects by enhancing dopamine activity in the mesolimbic dopamine system. The role of the dopamine transporter in terminating dopaminergic activity in synaptic neurotransmission suggests that variants of the dopamine transporter gene (DATI) might contribute to individual differences in vulnerability to addictive behavior. Our population-based association study investigated whether variants of DATI confer susceptibility to alcohol dependence in 293 alcoholics and clinically more homogeneous subgroups formed by: positive family history, early age-at-onset, delirium, withdrawal seizures, antisocial tendencies, type 1 and 2 alcoholics. Analyzing a VNTR polymorphism in the 3ʹ untranslated region of DATI, we found a significantly increased prevalence of the nine-repeat allele in 93 alcoholics displaying withdrawal seizures or delirium, compared with 93 ethnically matched nonalcoholic controls (p = 0.003; OR = 2.44; 95% confidence interval: 1.35–4.43). Our data provide evidence that a major genetic determinant of DATI influences vulnerability to severe alcohol withdrawal symptoms.