Genotype Influences In Vivo Dopamine Transporter Availability in Human Striatum
Abstract
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.
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The DAT1 C allele is associated with reduced transcription of the DAT1 gene.
“The DAT1 variant (rs40184, intron 14) is a SNP, and the C allele is associated with reduced transcription of the DAT1 gene (41).”
From Social disadvantage, genetic sensitivity, and children's telomere length (2014) · cites this paper as [41]
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- Authors
- Heinz, A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Heinz, A
- ORCID
- Heinz, A
- Venue
- Neuropsychopharmacology
- Published
- 2000-02
- Volume
- 22
- Issue
- 2
- Pages
- 133-139
- ISSN
- 0893-133X (ISSN-L)
- OpenAlex
- W2092868760
- Cited by
- 538
- References
- 51
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 7 · 2022: 6 · 2021: 12 · 2020: 10 · 2019: 19 · 2018: 14 · 2017: 19 · 2016: 17 · 2015: 20 · 2014: 29 · 2013: 34 · 2012: 34
- FWCI
- 8.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- dopamine transporter, VNTR polymorphism, 3' untranslated region, alcoholism, striatum, putamen, genotype-phenotype correlation, gene expression regulation, alcohol withdrawal
- MeSH terms
- Adult, Alcoholism, Carrier Proteins, Cocaine, Corpus Striatum, Genotype, Homozygote, Humans, Iodine Radioisotopes, Membrane Glycoproteins, Nerve Tissue Proteins, Polymorphism, Genetic, Reference Values, Temperance, Tomography, Emission-Computed, Single-Photon, Minisatellite Repeats, 3' Untranslated Regions, Membrane Transport Proteins, Dopamine Plasma Membrane Transport Proteins
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