ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2010
High regulatability favors genetic selection in SLC18A2, a vesicular monoamine transporter essential for life.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010. 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, 16 citations in OpenAlex.
- Epistatic evidence for gender-dependant slow neurotransmission signalling in substance use disorders: PPP1R12B versus PPP1R1B.EBioMedicine · 2020Article
- hVMAT2: A Target of Individualized Medication for Parkinson's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2016Article
- Genome-wide differential expression of synaptic long noncoding RNAs in autism spectrum disorder.Translational psychiatry · 2015Article
- Computational dissection of human episodic memory reveals mental process-specific genetic profiles.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Edaravone prevents neurotoxicity of mutant L166P DJ-1 in Parkinson's disease.Journal of molecular neuroscience : MN · 2013Article
- Human dopamine transporter gene: differential regulation of 18-kb haplotypes.Pharmacogenomics · 2013Article
- Vesicular integrity in Parkinson's disease.Current neurology and neuroscience reports · 2013Review
- Identification of an intronic cis-acting element in the human dopamine transporter gene.Molecular biology reports · 2012Article
- Article
- Genetic Variation in the Vesicular Monoamine Transporter: Preliminary Associations With Cognitive Outcomes After Severe Traumatic Brain Injury.The Journal of head trauma rehabilitationArticle
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
SLC18A2 encodes the vesicular monoamine transporter 2 protein that regulates neurotransmission and reduces cytosolic toxicity of monoamines. Deletion of this gene causes lethality in mice, and DNA sequence variation in this gene is associated with alcoholism and Parkinson's disease, among other disorders. The Caucasian SLC18A2 promoter has at least 20 haplotypes (A-T), with A representing two-thirds of 1460 chromosomes. It is not known why A is selected in the human lineage. To understand the selection, here we took a functional approach by investigating the regulations of 4 representative haplotypes (A, C, G, and T) by 17 agents. We show that 76.5% of the agents were able to regulate A but only 11.8-23.5% of them regulated the 3 other infrequent ones, observing a positive correlation between haplotype frequency and regulatability. Pathway and molecular analyses revealed five signaling hubs that regulate the four haplotypes differentially, probably through targeting the polymorphic core promoter region. These findings suggest that greater diversity of transcriptional regulations is the driving force for the haplotype selection in SLC18A2.
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