Association between harmful alcohol consumption behavior and dopamine transporter (DAT1) gene polymorphisms in a male Finnish population.
BACKGROUND
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.


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).


CONCLUSIONS
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.
Genetic Epidemiology, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Queensland, Australia. penelope.lind@qimr.edu.au
Penelope A
PA
Lind
C J Peter
CJ
Eriksson
Kirk C
KC
Wilhelmsen
D020413:3' Untranslated Regions; D000428:Alcohol Drinking / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005387:Finland; D005828:Genetics, Population; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D020080:Tandem Repeat Sequences
D020413:3' Untranslated Regions; D017931:DNA Primers; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human