THE DOPAMINE-D(2) RECEPTOR GENE - A GENETIC RISK FACTOR IN SUBSTANCE-ABUSE

Drug abuse has grown to epidemic proportions. Dopaminergic reward path ways 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 prevalen ce of the TaqI A1 variant of the DRD2 gene in 200 white patients hospi talized in the Addiction Treatment Unit of a Veterans Administration H ospital. While the prevalence of the D2A1 allele was not significantly increased over controls, it did increase from 21% in subjects with al cohol abuse only to 32% in subjects with alcohol dependence only, cons istent 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 vers us 29.0% of the 763 white controls (representing all white controls pu blished 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 regr ession analysis showed a highly significant association between multip le substance abuse based on money spent and the presence of the D2A1 a llele (P = 0.0003) and age of onset of abuse (P < 0.0001). D2A1 carrie rs exceeded D2A2A2 subjects for a history of being expelled from schoo l for fighting (P = 0.001), and of those ever jailed for violent crime s, 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 wer e both jailed for violent crime and expelled from school. We conclude that possession of the D2A1 allele is significantly associated with dr ug abuse/dependence and some aggressive behaviors.