The dopamine D₂ receptor gene: a genetic risk factor in substance abuse

Drug abuse has grown to epidemic proportions. Dopaminergic reward pathways have frequently been implicated in the etiology of drug addiction. To examine the possible role of genetic variants of the dopamine D₂ (DRD2) gene in susceptibility to drug abuse we determined the prevalence of the TaqI A1 variant of the DRD2 gene in 200 white patients hospitalized in the Addiction Treatment Unit of a Veterans Administration Hospital. While the prevalence of the D₂A1 allele was not significantly increased over controls, it did increase from 21% in subjects with alcohol abuse only to 32% in subjects with alcohol dependence only, consistent with other studies showing an association with the severity of alcoholism. By contrast, of 104 subjects with a discharge diagnosis of drug and alcohol abuse/dependence, 42.3% carried the D₂A1 allele versus 29.0% of the 763 white controls (representing all white controls published to date) (P = 0.006). Of those who spent more than $25/week on two or more substances, 56.9% carried the D₂A1 allele versus 28.2% of those abusing a single substance (P < 0.0005). Multiple logistic regression analysis showed a highly significant association between multiple substance abuse based on money spent and the presence of the D₂A1 allele (P = 0.0003) and age of onset of abuse (P < 0.0001). D₂A1 carriers exceeded D₂A2A2 subjects for a history of being expelled from school for fighting (P = 0.001), and of those ever jailed for violent crimes, 53.1% carried the D₂A1 allele versus 28.8% of those jailed for non-violent crimes (P = 0.011). This increased to 69.2% for those who were both jailed for violent crime and expelled from school. We conclude that possession of the D₂A1 allele is significantly associated with drug abuse/dependence and some aggressive behaviors.