MODIFICATION OF ALCOHOL-WITHDRAWAL BY THE A(9) ALLELE OF THE DOPAMINETRANSPORTER GENE

Objective: Determinants of individual vulnerability to alcohol withdra wal symptoms are largely unknown. Because of the substantial role of m onoaminergic transporters in limiting time and space effects of synapt ic neurotransmission, the dopamine transporter gene(DAT1;locus symbol: SLC6A3) was studied as a candidate gene possibly related to symptoms of uncomplicated alcohol withdrawal. Method: In 48 chronically intoxic ated alcoholics (diagnosed according to ICD-10), withdrawal symptoms w ere examined and the presence of a variable-number tandem repeat in th e 3' untranslated region of the DAT1 gene was determined. Results: Wit hdrawal syndromes were more pronounced in the 22 patients carrying the nine-copy repeat than in the 26 patients without this variant. Multip le regression analysis revealed that 4% of the variance of withdrawal was explained by this genotype, whereas 16% was due to the amount of a lcohol the patients reported having consumed in the month before detox ification. Conclusions: The A(9) allele of the dopamine transporter ge ne is associated with more severe effects of alcohol withdrawal, possi bly because of modifications of the brain's capacity to compensate for long-term effects of ethanol on cerebral function.