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The dopamine transporter gene SLC6A3: multidisease risks

The human dopamine transporter gene SLC6A3 has been consistently implicated in several neuropsychiatric diseases but the disease mechanism remains elusive. In this risk synthesis, we have concluded that SLC6A3 represents an increasingly recognized risk with a growing number of familial mutants assoc...

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Autores principales: Reith, Maarten E. A., Kortagere, Sandhya, Wiers, Corinde E., Sun, Hui, Kurian, Manju A., Galli, Aurelio, Volkow, Nora D., Lin, Zhicheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008071/
https://www.ncbi.nlm.nih.gov/pubmed/34650206
http://dx.doi.org/10.1038/s41380-021-01341-5
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author Reith, Maarten E. A.
Kortagere, Sandhya
Wiers, Corinde E.
Sun, Hui
Kurian, Manju A.
Galli, Aurelio
Volkow, Nora D.
Lin, Zhicheng
author_facet Reith, Maarten E. A.
Kortagere, Sandhya
Wiers, Corinde E.
Sun, Hui
Kurian, Manju A.
Galli, Aurelio
Volkow, Nora D.
Lin, Zhicheng
author_sort Reith, Maarten E. A.
collection PubMed
description The human dopamine transporter gene SLC6A3 has been consistently implicated in several neuropsychiatric diseases but the disease mechanism remains elusive. In this risk synthesis, we have concluded that SLC6A3 represents an increasingly recognized risk with a growing number of familial mutants associated with neuropsychiatric and neurological disorders. At least five loci were related to common and severe diseases including alcohol use disorder (high activity variant), attention-deficit/hyperactivity disorder (low activity variant), autism (familial proteins with mutated networking) and movement disorders (both regulatory variants and familial mutations). Association signals depended on genetic markers used as well as ethnicity examined. Strong haplotype selection and gene-wide epistases support multimarker assessment of functional variations and phenotype associations. Inclusion of its promoter region’s functional markers such as DNPi (rs67175440) and 5’VNTR (rs70957367) may help delineate condensate-based risk action, testing a locus-pathway-phenotype hypothesis for one gene-multidisease etiology.
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spelling pubmed-90080712022-05-01 The dopamine transporter gene SLC6A3: multidisease risks Reith, Maarten E. A. Kortagere, Sandhya Wiers, Corinde E. Sun, Hui Kurian, Manju A. Galli, Aurelio Volkow, Nora D. Lin, Zhicheng Mol Psychiatry Article The human dopamine transporter gene SLC6A3 has been consistently implicated in several neuropsychiatric diseases but the disease mechanism remains elusive. In this risk synthesis, we have concluded that SLC6A3 represents an increasingly recognized risk with a growing number of familial mutants associated with neuropsychiatric and neurological disorders. At least five loci were related to common and severe diseases including alcohol use disorder (high activity variant), attention-deficit/hyperactivity disorder (low activity variant), autism (familial proteins with mutated networking) and movement disorders (both regulatory variants and familial mutations). Association signals depended on genetic markers used as well as ethnicity examined. Strong haplotype selection and gene-wide epistases support multimarker assessment of functional variations and phenotype associations. Inclusion of its promoter region’s functional markers such as DNPi (rs67175440) and 5’VNTR (rs70957367) may help delineate condensate-based risk action, testing a locus-pathway-phenotype hypothesis for one gene-multidisease etiology. Nature Publishing Group UK 2021-10-14 2022 /pmc/articles/PMC9008071/ /pubmed/34650206 http://dx.doi.org/10.1038/s41380-021-01341-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Reith, Maarten E. A.
Kortagere, Sandhya
Wiers, Corinde E.
Sun, Hui
Kurian, Manju A.
Galli, Aurelio
Volkow, Nora D.
Lin, Zhicheng
The dopamine transporter gene SLC6A3: multidisease risks
title The dopamine transporter gene SLC6A3: multidisease risks
title_full The dopamine transporter gene SLC6A3: multidisease risks
title_fullStr The dopamine transporter gene SLC6A3: multidisease risks
title_full_unstemmed The dopamine transporter gene SLC6A3: multidisease risks
title_short The dopamine transporter gene SLC6A3: multidisease risks
title_sort dopamine transporter gene slc6a3: multidisease risks
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008071/
https://www.ncbi.nlm.nih.gov/pubmed/34650206
http://dx.doi.org/10.1038/s41380-021-01341-5
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