title: Common human 5' dopamine transporter (SLC6A3) haplotypes yield varying expression levels in vivo.
abstract: 1. Individuals display significant differences in their levels of expression of the dopamine transporter (DAT; SLC6A3). These differences in DAT are strong candidates to contribute to individual differences in motor, mnemonic and reward functions. To identify "cis"-acting genetic mechanisms for these individual differences, we have sought variants in 5' aspects of the human DAT gene and identified the haplotypes that these variants define. 2. We report (i) significant relationships between 5' DAT haplotypes and human individual differences in ventral striatal DAT expression assessed in vivo using [(11)C] cocaine PET and (ii) apparent confirmation of these results in studies of DAT expression in postmortem striatum using [(3)H] carboxyflurotropane binding. 3. These observations support the idea that cis-acting variation in 5' aspects of the human DAT/SLC6A3 locus contributes to individual differences in levels of DAT expression in vivo. 5' DAT variation is thus a good candidate to contribute to individual differences in a number of human phenotypes.
authors.affiliation: Molecular Neurobiology Branch, NIDA-IRP, NIH, DHSS, Box 5180, Baltimore, Maryland 21224, USA.
authors.forename: Tomas
authors.initials: T
authors.lastname: Drgon
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Lin
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
authors.forename: Joanna
authors.initials: J
authors.lastname: Fowler
authors.forename: Johnfn
authors.initials: J
authors.lastname: Pablo
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Mash
authors.forename: Nora
authors.initials: N
authors.lastname: Volkow
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
mesh_terms: D024506:5' Flanking Region; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism; D001479:Basal Ganglia / Q000378:metabolism; D001483:Base Sequence; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human