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 D2 receptor density in vivo in human striatum. Low D2 receptor binding in vivo has been found to associate with alcohol/substance dependence. It has been suggested that the A1 allele of human D2 receptor gene might be associated to a specific type of alcoholism and possibly to a reduced D2 receptor density in vitro. We have determined D2 dopamine receptor-binding density (Bmax), affinity (Kd) and availability (Bmax/Kd) 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 Kd 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.
Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.
T
T
Pohjalainen
J O
JO
Rinne
K
K
Någren
P
P
Lehikoinen
K
K
Anttila
E K
EK
Syvälahti
J
J
Hietala
D000328:Adult; D000483:Alleles; D001921:Brain / Q000000981:diagnostic imaging; D001923:Brain Chemistry / Q000235:genetics*; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D005387:Finland; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020891:Raclopride; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012457:Salicylamides; D014055:Tomography, Emission-Computed
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride