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Common Human 5′ Dopamine Transporter (SLC6A3) Haplotypes Yield Varying Expression Levels In Vivo

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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 [11C] cocaine PET and (ii) apparent confirmation of these results in studies of DAT expression in postmortem striatum using [3H] 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.

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ACKNOWLEDGMENTS

We acknowledge support from NIDA-IRP, support for imaging studies by NIDA grants DA09490-01, DA 7092-01 and DA00280, support for radiologand binding studies from DA 06227, assistance from Judith Hess, Felly Carillo and Donna Walther with human sample characterization and preparation, and NIAAA and COGA investigators for generously making DNAs from COGA participants available.

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Authors and Affiliations

  1. Molecular Neurobiology Branch, NIDA-IRP, NIH, DHSS, Box 5180, Baltimore, Maryland, 21224, USA

    Tomas Drgon & George R. Uhl

  2. Brookhaven National Laboratories, Upton, New York, USA

    Tomas Drgon, Zhicheng Lin, Gene-Jack Wang & Joanna Fowler

  3. Department of Neurology, University of Miami School of Medicine, Miami, Florida, USA

    Johnfn Pablo & Deborah C. Mash

  4. Office of the Director, NIDA, NIH, DHSS, Rockville, Maryland, USA

    Nora Volkow

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  1. Tomas Drgon
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  2. Zhicheng Lin
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Correspondence to George R. Uhl.

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Drgon, T., Lin, Z., Wang, GJ. et al. Common Human 5′ Dopamine Transporter (SLC6A3) Haplotypes Yield Varying Expression Levels In Vivo . Cell Mol Neurobiol 26, 873–887 (2006). https://doi.org/10.1007/s10571-006-9014-3

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