Genotype influences in vivo dopamine transporter availability in human striatum.
In vivo availability of striatal dopamine transporter (DAT) protein has been reported to be reduced among alcoholics, and allelic variation of the DAT gene (SLC6A3) has been associated with severity of alcohol withdrawal. We examined the VNTR polymorphism of the 3' untranslated region of SLC6A3 and DAT protein availability in 14 abstinent alcoholics and 11 control subjects. Single photon emission computed tomography (SPECT) and plasma levels of the radioligand [I-123]beta-CIT were used to quantify DAT protein availability. Individuals with the 9-repeat/10-repeat genotype had a mean 22% reduction of DAT protein availability in putamen compared with 10-repeat homozygous individuals (t = 2.14, df = 23, p < .05). Consistent with earlier studies, alcoholism, per se, was not significantly associated with either DAT availability or DAT genotype. These findings suggest that the VNTR polymorphism of the DAT gene effects translation of the DAT protein. This effect may explain a variety of clinical associations that have been reported with this polymorphism.
Heinz
A
A
Clinical Brain Disorders Branch, NIMH, National Institutes of Health, Bethesda, MD 20892-1379, USA.
Goldman
D
D
Jones
D W
DW
Palmour
R
R
Hommer
D
D
Gorey
J G
JG
Lee
K S
KS
Linnoila
M
M
Weinberger
D R
DR
D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D018598:Minisatellite Repeats; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D012016:Reference Values; D013695:Temperance; D015899:Tomography, Emission-Computed, Single-Photon
D020413:3' Untranslated Regions; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine