The A1 allele of the human D₂ dopamine receptor gene predicts low D₂ receptor availability in healthy volunteers

Abstract

Positron emission tomography (PET) studies have revealed significant interindividual variation in dopamine D₂ receptor density in vivo in human striatum.¹ Low D₂ receptor binding in vivo has been found to associate with alcohol/substance dependence.^2–6 It has been suggested that the A1 allele of human D₂ receptor gene might be associated to a specific type of alcoholism⁷ and possibly to a reduced D₂ receptor density in vitro.⁸ We have determined D₂ dopamine receptor-binding density (B_max), affinity (K_d) and availability (B_max/K_d) in 54 healthy Finnish volunteers using PET and [¹¹C]raclopride in order to determine whether the A1 allele is associated with a ‘baseline’ difference in D₂ receptor characteristics in vivo. A statistically significant reduction in D₂ receptor availability reflecting an alteration in receptor density was observed in the A1/A2 genotype group compared to the A2/A2 group. There was no difference in apparent K_d between the two groups. In conclusion, the association between the A1 allele and low D₂ receptor availability in healthy subjects indicates that the A1 allele of the TaqIA polymorphism might be in linkage disequilibrium with a mutation in the promoter/regulatory gene element that affects dopamine D₂ receptor expression. This study provides an in vivo neurobiological correlate to the A1 allele in healthy volunteers.