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

Positron emission tomography (PET) studies have revealed significant interindividual variation in dopamine D-2 receptor density in vivo in human striatum.(1) Low D-2 receptor binding in vivo has been found to associate with alcohol/substance dependence,(2-6) It has been suggested that the Al allele of human D-2 receptor gene might be associated to a specific type of alcoholism(7) and possibly to a reduced D-2 receptor density in vitro.(8) We have determined D-2 dopamine receptor-binding density (B-max), affinity (K-d) and availability (B-max/K-d) in 54 healthy Finnish volunteers using PET and [C-11]raclopride in order to determine whether the A1 allele is associated with a 'baseline' difference in D-2 receptor characteristics in vivo. A statistically significant reduction in D-2 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 D-2 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 D-2 receptor expression. This study provides an in vivo neurobiological correlate to the A1 allele in healthy volunteers.