Homozygosity at the dopamine DRD3 receptor gene in cocaine dependence

We examined the hypothesis that the dopamine D-3 receptor gene (DRD3) is a susceptibility factor for cocaine dependence. The MscI/BalI polymorphism of the DRD3 gene was examined in 47 Caucasian subjects with cocaine dependenc e and 305 Caucasian controls. Based on prior studies with a range of psychi atric disorders we hypothesized there would be a decrease in the frequency of the 12 genotype in the patient sample (increased homozygosity). We obser ved a significant decrease in the frequency of 12 heterozygotes in subjects with cocaine dependence (29.8%) vs controls (46.9%) (P less than or equal to 0.028). This percentage was still fewer in those who had chronically use d cocaine for more than 10 years (25%), or more than 15 years (21.5%). The DRD3 gene accounted for 1.64% of the variance of cocaine dependence. The DR D2 gene had an independent and additive effect on cocaine dependence. These findings support a modest role of the DRD3 gene in susceptibility to cocai ne dependence.