Ethanol-induced dopamine (DA) release in the mesolimbic system may reinforce excessive alcohol intake and the progression of alcohol dependence. Within this reward system, the DA transporter (DAT1) plays a key role in the regulation of dopaminergic neurotransmission through presynaptic DA reuptake.Objective
This study investigated whether DAT1 genetic variation was associated with either alcohol consumption behavior or alcohol dependence in a Finnish cohort.Methods
Eight single nucleotide polymorphisms and a frequently studied 3′-untranslated region 40-bp variable number tandem repeat were genotyped in unrelated male Finnish participants selected from alcoholism clinical treatment facilities (n=104), or through the Finnish Population Register (n=201). All participants completed the Alcohol Use Disorder Identification Test.Main results
We found significant evidence that the synonymous exon 2 rs6350 variant was positively associated with both alcohol consumption behavior (P=0.0004) and problem drinking (G allele, odds ratio: 3.63, 95% confidence interval: 1.22–10.78). A second single nucleotide polymorphism, rs463379 (intron 4), was negatively associated with alcohol dependence (A allele, odds ratio: 0.61, 95% confidence interval: 0.39–0.94). However, two-locus haplotypic analysis of rs6350–rs463379 did not further increase the strength of association with the quantitative Alcohol Use Disorder Identification Test score trait (P=0.0024).Conclusion
The present findings suggest that DAT1 genetic variation influences drinking behavior in our Finnish population, where the rs6350 A and rs463379 G alleles provide a protective role against high alcohol consumption and alcohol dependence, respectively. A systematic search for DAT1 variants that affect gene function or expression in the Finnish and other populations is warranted.