Dopamine transporter genotype influences N-acetyl-aspartate in the left putamen.
BACKGROUND
Dopaminergic activity in the brain is modulated by the dopamine transporter (DAT). Several lines of evidence suggest that a variable number of tandem repeats (VNTR) polymorphism of the DAT1 gene (SLC6A3) influences its gene expression. The aim of this study was to determine whether the DAT1VNTR polymorphism alters the metabolic ratios NAA/Cho, NAA/Cr, Cho/Cr and Ins/Cr in the left dorsolateral prefrontal cortex, anterior cingulate cortex, and putamen in healthy subjects and psychiatric patients irrespective of clinical diagnosis.


METHODS
Sixty-four individuals (30 patients with bipolar disorder, 18 patients with obsessive-compulsive disorder, and 16 healthy subjects) participated in the study. The 3'-UTR VNTR polymorphism of DAT1 (SLC6A3) gene was genotyped in all individuals. (1)H-MRS was performed in the above-mentioned brain regions.


RESULTS
The individuals with the homozygous DAT1 10-repeat genotype presented significantly higher ratios of NAA/Cho and NAA/Cr in the left putamen compared to the group of individuals with the 9/9-repeat or 9/10-repeat genotype.


CONCLUSIONS
The VNTR polymorphism of the DAT1-gene modulates NAA/Cho and NAA/Cr in the left putamen independent of psychiatric diagnosis status. These results suggest an association of DAT1 VNTR polymorphism, dopaminergic activity, and neuronal function in putamen.
Scherk
Harald
H
Department of Psychiatry and Psychotherapy, Georg-August-University Goettingen, Goettingen, Germany. hscherk@uni-goettingen.de
Backens
Martin
M
Schneider-Axmann
Thomas
T
Kraft
Susanne
S
Kemmer
Claudia
C
Usher
Juliana
J
Reith
Wolfgang
W
Falkai
Peter
P
Meyer
Jobst
J
Gruber
Oliver
O
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001714:Bipolar Disorder / Q000235:genetics*; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D004292:Dominance, Cerebral / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D005838:Genotype; D006179:Gyrus Cinguli / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D017397:Prefrontal Cortex / Q000378:metabolism; D011699:Putamen / Q000378:metabolism*; D012016:Reference Values; D055815:Young Adult
D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline