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Substance abuse vulnerability and D2 receptor genes

G Uhl¹, K Blum, E Noble

¹Laboratory of Molecular Neurobiology, National Institute on Drug Abuse, Baltimore, MD 21224.

Trends in Neurosciences

|March 1, 1993

Summary

Genetic variations in the dopamine D2 receptor (DRD2) gene, specifically TaqIA1 and B1 markers, are linked to substance abuse vulnerability. Meta-analyses support DRD2 gene variants contributing to differences in alcoholism and polysubstance abuse susceptibility.

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Area of Science:

Neuroscience
Genetics
Psychiatry

Background:

Dopamine systems play a crucial role in the effects of various substances.
Individual genetic differences in dopaminergic neurotransmission may underlie variations in substance abuse vulnerability.

Purpose of the Study:

To investigate the association between dopamine D2 receptor (DRD2) gene polymorphisms (TaqIA1 and B1 markers) and substance abuse behaviors.
To determine if DRD2 gene variants contribute to inter-individual differences in vulnerability to substance abuse.

Main Methods:

Analysis of restriction fragment length polymorphism (RFLP) markers TaqIA1 and B1 at the DRD2 gene locus.
Comparison of marker frequencies in individuals with substance abuse behaviors versus control groups.
Meta-analysis of existing controlled studies.

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Main Results:

The TaqIA1 and B1 RFLP markers at the DRD2 gene locus were found more frequently in substance abusers than in control individuals in most studies.
Meta-analyses of available data suggest a consistent association between DRD2 gene variants and increased vulnerability to alcoholism and polysubstance abuse.

Conclusions:

DRD2 gene variants, identified by TaqIA1 and B1 markers, are associated with substance abuse behaviors.
Meta-analyses support the role of DRD2 gene variants in inter-individual differences in vulnerability to alcoholism and polysubstance abuse.