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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
50
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pubmed:dateCreated |
2006-12-13
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pubmed:abstractText |
The norepinephrine transporter critically regulates both neurotransmission and homeostasis of norepinephrine in the nervous system. In this study, we report a previously uncharacterized and common A/T polymorphism at -3081 upstream of the transcription initiation site of the human norepinephrine transporter gene [solute carrier family 6, member 2 (SLC6A2)]. Using both homologous and heterologous promoter-reporter constructs, we found that the -3081(T) allele significantly decreases promoter function compared with the A allele. Interestingly, this T allele creates a new palindromic E2-box motif that interacts with Slug and Scratch, neural-expressed transcriptional repressors binding to the E2-box motif. We also found that both Slug and Scratch repress the SLC6A2 promoter activity only when it contains the T allele. Finally, we observed a significant association between the -3081(A/T) polymorphism and attention-deficit hyperactivity disorder (ADHD), suggesting that anomalous transcription factor-based repression of SLC6A2 may increase risk for the development of attention-deficit hyperactivity disorder and other neuropsychiatric diseases.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-10206236,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-10638067,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-10684912,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-10769386,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-11857564,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-11994736,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-12140790,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-12196911,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-12210284,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-12456942,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-14110752,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-14681910,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-15063099,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-15337696,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-15556286,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-15717291,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-16255080,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-16773660,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-2008212,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17146058-9837830
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0027-8424
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pubmed:author |
pubmed-author:AndersonSusan LSL,
pubmed-author:BlakelyRandy DRD,
pubmed-author:CohenBruce MBM,
pubmed-author:GizerIanI,
pubmed-author:HahnMaureen KMK,
pubmed-author:JoungYoosookY,
pubmed-author:KimChun-HyungCH,
pubmed-author:KimKwang-SooKS,
pubmed-author:Mazei-RobinsonMichelle SMS,
pubmed-author:RobertsonDavidD,
pubmed-author:SteeleAngela HAH,
pubmed-author:TeicherMartin HMH,
pubmed-author:WaldmanIrwin DID
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pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
19164-9
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:17146058-Alleles,
pubmed-meshheading:17146058-Attention Deficit Disorder with Hyperactivity,
pubmed-meshheading:17146058-Base Sequence,
pubmed-meshheading:17146058-DNA,
pubmed-meshheading:17146058-Gene Expression Regulation,
pubmed-meshheading:17146058-Humans,
pubmed-meshheading:17146058-Norepinephrine Plasma Membrane Transport Proteins,
pubmed-meshheading:17146058-Polymorphism, Genetic,
pubmed-meshheading:17146058-Promoter Regions, Genetic,
pubmed-meshheading:17146058-Protein Binding,
pubmed-meshheading:17146058-Transcription, Genetic,
pubmed-meshheading:17146058-Transcription Factors,
pubmed-meshheading:17146058-Zinc Fingers
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pubmed:year |
2006
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pubmed:articleTitle |
A polymorphism in the norepinephrine transporter gene alters promoter activity and is associated with attention-deficit hyperactivity disorder.
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pubmed:affiliation |
Molecular Neurobiology, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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