Haplotypes at the DRD2 locus and severe alcoholism

Area of Science:

• Neurogenetics
• Psychiatric Genetics
• Molecular Psychiatry

Background:

• Conflicting findings exist regarding the association between the TaqI A allele of the dopamine D(2) receptor (DRD2) gene and alcoholism.
• Previous studies may be limited by not assessing alcoholism severity or screening controls for substance use.

Purpose of the Study:

• To investigate the association between DRD2 gene polymorphisms and severe alcoholism.
• To address limitations of prior studies by examining alcoholism severity and using screened controls.

Main Methods:

• Genotyping of five diallelic sites across the DRD2 gene in Caucasian alcoholics (n=92) and substance-screened controls (n=85).
• Analysis of allele frequencies, genotype combinations, and haplotype disequilibria.
• Assessment for Hardy-Weinberg equilibrium.

Main Results:

• Minor alleles at the TaqI A (3'-untranslated) and two intronic sites (TaqI B, intron 6) of the DRD2 gene were strongly associated with alcoholism.
• A higher frequency of heterozygote haplotype combinations (A1/A2 B1/B2 T/G) was observed in alcoholics compared to controls.
• No association was found for exon 7 and promoter alleles; Hardy-Weinberg equilibrium was maintained.

Conclusions:

• The findings provide significant evidence for the association of minor alleles in untranslated DRD2 gene regions and their haplotypes with a more severe alcoholic phenotype.
• These results suggest specific DRD2 genetic markers may contribute to alcoholism susceptibility.