Source:http://linkedlifedata.com/resource/pubmed/id/17185747
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2007-2-1
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pubmed:abstractText |
Wide variation in glucocorticoid (Gc) sensitivity exists between individuals which may influence susceptibility to, and treatment response of, inflammatory diseases. To determine a genetic fingerprint of Gc sensitivity 100 healthy human volunteers were polarized into the 10% most Gc-sensitive and 10% most Gc-resistant following a low dose dexamethasone (0.25 mg) suppression test. Gene expression profiling of primary lymphocytes identified the 98 most significantly Gc regulated genes. These genes were used to build a subnetwork of Gc signaling, with 54 genes mapping as nodes, and 6 non-Gc regulated genes inferred as signaling nodes. Twenty four of the 98 genes showed a difference in Gc response in vitro dependent on the Gc sensitivity of their donor individuals in vivo. A predictive model was built using both partial least squares discriminate analysis and support vector machines that predicted donor glucocorticoid sensitivity with 87% accuracy. Discriminating genes included bone morphogenetic protein receptor, type II (BMPRII). Transfection studies showed that BMPRII modulated Gc action. These studies reveal a broad base of gene expression that predicts Gc sensitivity and determine a Gc signaling network in human primary T lymphocytes. Furthermore, this combined gene profiling, and functional analysis approach has identified BMPRII as a modulator of Gc signaling.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1530-6860
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pubmed:author |
pubmed-author:BaertR JRJ,
pubmed-author:BettsJoannaJ,
pubmed-author:ClaytonChrisC,
pubmed-author:DonnRachelleR,
pubmed-author:FarrowStuartS,
pubmed-author:GrahamSimonS,
pubmed-author:RayDavidD,
pubmed-author:ScottLaurieL,
pubmed-author:StevensAdamA,
pubmed-author:StevensRichardR,
pubmed-author:WangJixianJ,
pubmed-author:WarnockLindaL,
pubmed-author:WorthingtonJaneJ
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pubmed:issnType |
Electronic
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
402-14
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17185747-Adult,
pubmed-meshheading:17185747-Bone Morphogenetic Protein Receptors, Type II,
pubmed-meshheading:17185747-Cluster Analysis,
pubmed-meshheading:17185747-Dexamethasone,
pubmed-meshheading:17185747-Female,
pubmed-meshheading:17185747-Gene Expression Profiling,
pubmed-meshheading:17185747-Gene Expression Regulation,
pubmed-meshheading:17185747-Glucocorticoids,
pubmed-meshheading:17185747-Humans,
pubmed-meshheading:17185747-Least-Squares Analysis,
pubmed-meshheading:17185747-Male,
pubmed-meshheading:17185747-Middle Aged,
pubmed-meshheading:17185747-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:17185747-T-Lymphocytes
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pubmed:year |
2007
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pubmed:articleTitle |
Use of gene expression profiling to identify a novel glucocorticoid sensitivity determining gene, BMPRII.
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pubmed:affiliation |
Centre for Molecular Medicine, University of Manchester, Oxford Rd., Manchester, M13 9PT, UK.
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pubmed:publicationType |
Journal Article
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