D2 receptor gene variants and substance abuse liability

Influences on dopaminergic neurotransmission appear to be key neurobiological substrates for the acute effects, and conceivably for the abuse liability, of several addictive drugs. Genetic factors partly responsible for inter-individual differences in vulnerability to substance abuse could thus include variants of genes encoding dopaminergic proteins. The D₂ dopamine receptor (DRD₂) gene locus displays polymorphic genetic markers. Two of these markers, TaqI 'A1' and 'B1' Restriction Fragment Length Polymorphisms (RFLP), appear to identify a DRD₂ gene variant associated with enhanced vulnerability to substance abuse behaviors in caucasians. Most, but not all, studies of alcoholics and polysubstance abusers describe higher frequencies of the DRD₂ allele displaying A1 and B1 markers among substance abusers than control individuals. These findings could conceivably be confounded by RFLP frequency differences in distinct caucasian ethnic groups; no study has yet identified substance abusers or controls by sampling randomly from the general population. However, meta-analyses of the data from studies published to data are consistent with contributions by DRD₂ gene variants to inter-individual differences in vulnerability to alcoholism and polysubstance abuse in man.