COMT Val158Met genotype does not alter cortical or striatal dopamine D2 receptor availability in vivo.
OBJECTIVE
Catechol-O-methyl transferase (COMT) is a pivotal regulator of brain dopamine function with a region-specific role. COMT is important in dopamine elimination in the prefrontal cortex, whereas dopamine reuptake is the main mechanism for synaptic removal of dopamine in the striatum. We studied whether the functional COMT gene polymorphism (Val158Met) associates with altered dopamine D2 receptor binding characteristics in vivo hypothesizing an effect in the cortex but not in the striatum.


METHODS
Samples of 38 and 45 Finnish healthy subjects scanned previously with PET and the D2/D3 receptor radioligands [(11)C]FLB457 or [(11)C]raclopride, respectively, were genotyped for the Val158Met polymorphism.


RESULTS
No significant associations were found between the Val158Met genotype and D2 receptor binding characteristics in the cortex or the striatum as measured with [(11)C]FLB457 and [(11)C]raclopride, respectively.


CONCLUSIONS
COMT genotype is not related with alterations in baseline D2 receptor availability in vivo in the cortex or the striatum. This information is useful for the interpretation of genetic studies on COMT in neuropsychiatry.
Hirvonen
Mika M
MM
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
Någren
Kjell
K
Rinne
Juha O
JO
Pesonen
Ullamari
U
Vahlberg
Tero
T
Hagelberg
Nora
N
Hietala
Jarmo
J
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002540:Cerebral Cortex / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D003710:Demography; D005838:Genotype; D006801:Humans; D008024:Ligands; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
D008024:Ligands; D017448:Receptors, Dopamine D2; D002394:Catechol O-Methyltransferase