ArticlePharmacogenomics2013
Human dopamine transporter gene: differential regulation of 18-kb haplotypes.
Article in Pharmacogenomics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Presence of recombination hotspots throughout SLC6A3.PloS one · 2019Trial
- Association ofFrontiers in psychiatry · 2023Article
- The dopamine transporter gene SLC6A3: multidisease risks.Molecular psychiatry · 2022Article
- Epistatic evidence for gender-dependant slow neurotransmission signalling in substance use disorders: PPP1R12B versus PPP1R1B.EBioMedicine · 2020Article
- Identification of HIVEP2 as a dopaminergic transcription factor related to substance use disorders in rats and humans.Translational psychiatry · 2019Article
- Intragenic Transcriptional cis-Antagonism Across SLC6A3.Molecular neurobiology · 2019Article
- Activation of RHO-1 in cholinergic motor neurons competes with dopamine signalling to control locomotion.PloS one · 2018Article
- hVMAT2: A Target of Individualized Medication for Parkinson's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2016Article
- Increased Nigral SLC6A3 Activity in Schizophrenia Patients: Findings From the Toronto-McLean Cohorts.Schizophrenia bulletin · 2016Article
- Epigenetic Regulation of Dopamine Transporter mRNA Expression in Human Neuroblastoma Cells.Neurochemical research · 2015Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
aimSince previous functional studies of short haplotypes and polymorphic sites of SLC6A3 have shown variant-dependent and drug-sensitive promoter activity, this study aimed to understand whether a large SLC6A3 regulatory region, containing these small haplotypes and polymorphic sites, can display haplotype-dependent promoter activity in a drug-sensitive and pathway-related manner. MATERIALS &
methodsBy creating and using a single copy number luciferase-reporter vector, we examined regulation of two different SLC6A3 haplotypes (A and B) of the 5´ 18-kb promoter and two known downstream regulatory variable number tandem repeats by 17 drugs in four different cellular models.
resultsThe two regulatory haplotypes displayed up to 3.2-fold difference in promoter activity. The regulations were drug selective (37.5% of the drugs showed effects), and both haplotype and cell type dependent. Pathway analysis revealed at least 13 main signaling hubs targeting SLC6A3, including histone deacetylation, AKT, PKC and CK2 α-chains.
conclusionSLC6A3 may be regulated via either its promoter or the variable number tandem repeats independently by specific signaling pathways and in a haplotype-dependent manner. Furthermore, we have developed the first pathway map for SLC6A3 regulation. These findings provide a framework for understanding complex and variant-dependent regulations of SLC6A3.
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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.