ArticleProceedings of the National Academy of Sciences of the United States of America2006
A dopamine transporter gene functional variant associated with cocaine abuse in a Brazilian sample.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 176 citations in OpenAlex.
- Multicenter analysis of the SLC6A3/DAT1 VNTR haplotype in persistent ADHD suggests differential involvement of the gene in childhood and persistent ADHD.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2010Pooled it
- Candidate gene studies of ADHD: a meta-analytic review.Human genetics · 2009Pooled it
- Pharmacogenetic role of dopamine transporter (SLC6A3) variation on response to disulfiram treatment for cocaine addiction.The American journal on addictions · 2019Trial
- Presence of recombination hotspots throughout SLC6A3.PloS one · 2019Trial
- Polymorphism of the dopamine transporter type 1 gene modifies the treatment response in Parkinson's disease.Brain : a journal of neurology · 2015Trial
- Amphetamine sensitization alters reward processing in the human striatum and amygdala.PloS one · 2014Trial
- Modulation of orbitofrontal response to amphetamine by a functional variant of DAT1 and in vitro confirmation.Molecular psychiatry · 2011Trial
- PGx-BasedCurrent neuropharmacology · 2026Article
- Malnutrition in Substance Use Disorders: A Critical Issue in Their Treatment and Recovery.Healthcare (Basel, Switzerland) · 2025Review
- Association of the SLC6A3 Gene rs2652511 Polymorphism with Methamphetamine Abuse Disorder in the Iranian Population.Addiction & health · 2025Article
- The Relationship between Gene SLC6A3 Variable Number of Tandem Repeat (VNTR) and Attention-Deficit/Hyperactivity Disorder.Iranian journal of psychiatry · 2024Article
- A novel hypervariable variable number tandem repeat in the dopamine transporter gene (Life science alliance · 2023Article
- Functional SLC6A3 polymorphisms differentially affect autism spectrum disorder severity: a study on Indian subjects.Metabolic brain disease · 2022Article
- The dopamine transporter gene SLC6A3: multidisease risks.Molecular psychiatry · 2022Article
- A systems omics-based approach to decode substance use disorders and neuroadaptations.Neuroscience and biobehavioral reviews · 2021Review
- Association of Dopamine Transporter Gene with Heroin Dependence in an Indian Subpopulation from Manipur.Journal of molecular neuroscience : MN · 2021Article
- Dopamine Related Genes Differentially Affect Declarative Long-Term Memory in Healthy Humans.Frontiers in behavioral neuroscience · 2020Article
- Non-coding genetic variation shaping mental health.Current opinion in psychology · 2019Review
- Intragenic Transcriptional cis-Antagonism Across SLC6A3.Molecular neurobiology · 2019Article
- Genetics of cocaine and methamphetamine consumption and preference in Drosophila melanogaster.PLoS genetics · 2019Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
Abstract
The dopamine (DA) transporter DAT1 is a major target bound by cocaine in brain. We examined the influence of functional genetic variants in DAT1 on cocaine addiction. Repeat polymorphisms, including a 30-bp variable-number tandem repeat (VNTR) in intron 8 (Int8 VNTR) with two common alleles, were genotyped in cocaine-dependent abusers (n = 699) and in controls with no past history of drug abuse (n = 866) from São Paulo, Brazil. Positive association was observed with allele 3 of the Int8 VNTR and cocaine abuse (allele odds ratio = 1.2, 95% confidence interval = 1.01-1.37, P = 0.036; 3/3 homozygote odds ratio = 1.45, 95% confidence interval = 1.18-1.78, P = 0.0008). Population stratification was assessed and did not affect the results. Haplotypic analyses using additional polymorphisms indicated that the Int8 VNTR is responsible for the observed association. Functional analyses in reporter-gene constructs, demonstrated that allele 3 mediates significant (P < 0.05) but small reduced expression compared with the "protective" allele 2. This difference increased when 1 and 10 muM cocaine was added to the cell culture ( approximately 40% reduction of the 3 allele expression versus the 2 allele). The 3 allele also demonstrated approximately 3-fold-increased expression over the 2 allele in response to KCl plus forskolin challenge. We demonstrate a robust association between cocaine dependence and a VNTR allele in SLC6A3, conferring a small but detectable effect, and we show that this VNTR may be functional. This study suggests that DAT1 gene variation may play a role in cocaine dependence etiology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.