Dopamine transporter gene polymorphisms are not associated with polysubstance abuse

Abstract

Susceptibility to drug and alcohol abuse is presently thought to arise from a combination of biological, psychological, and social factors. Genetic contributions to substance use, abuse, and dependence are supported by family, twin, and adoption studies (Pedersen 1984; Cadoret et al 1987; Luthar et al 1992). Most substances that are abused by humans can enhance dopamine activity in mesolimbic/mesocortieal circuits important for behavioral reward and reinforcement (Di Chiara and lmperato 1988). Such neurobiological findings have stimulated interest in the possibility that interindividual differences in the structure or expression of genes of dopaminergic neurotransmission could contribute to individual differences in vulnerability to substance abuse. Interest is also spurred by evidence that variation at the dopamine D2 receptor gene may help to determine such vulnerability (Blum et al 1990; Uhl et al 1992; Smith et al 1992). Although the effect of a single gene is unlikely to account for the entire genetic contribution to substance abuse vulnerability, these results lend credence to searches for possible involvement of other dopaminergic genes. The dopamine transporter (DATI) gene encodes a dopamineceU-specific protein that is the direct target of cocaine action (Ritz et al 1987). DATI is thus a candidate gene for involvement in substance abuse vulnerability. We have recently cloned human DATI complementary DNAs, and identified a 5' polymorphic restriction fragment length polymorphism (RFLP) (Vandenbergh et al 1992a) and a 3' variable number tandem repeat (VNTR) marker for the human DATI gene locus (Vandenbergh et al 1992b). These advances now allow study of possible allelic association of these human DATI gene markers with substance abuse.