Interactions between Glucocorticoid Treatment and Cis-Regulatory Polymorphisms Contribute to Cellular Response Phenotypes

Glucocorticoids (GCs) mediate physiological responses to environmental stress and are commonly used as pharmaceuticals. GCs act primarily through the GC receptor (GR, a transcription factor). Despite their clear biomedical importance, little is known about the genetic architecture of variation in GC...

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Main Authors:	Maranville, Joseph C., Luca, Francesca, Richards, Allison L., Wen, Xiaoquan, Witonsky, David B., Baxter, Shaneen, Stephens, Matthew, Di Rienzo, Anna
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131293/

id	pubmed-3131293
recordtype	oai_dc
spelling	pubmed-31312932011-07-12 Interactions between Glucocorticoid Treatment and Cis-Regulatory Polymorphisms Contribute to Cellular Response Phenotypes Maranville, Joseph C. Luca, Francesca Richards, Allison L. Wen, Xiaoquan Witonsky, David B. Baxter, Shaneen Stephens, Matthew Di Rienzo, Anna Research Article Glucocorticoids (GCs) mediate physiological responses to environmental stress and are commonly used as pharmaceuticals. GCs act primarily through the GC receptor (GR, a transcription factor). Despite their clear biomedical importance, little is known about the genetic architecture of variation in GC response. Here we provide an initial assessment of variability in the cellular response to GC treatment by profiling gene expression and protein secretion in 114 EBV-transformed B lymphocytes of African and European ancestry. We found that genetic variation affects the response of nearby genes and exhibits distinctive patterns of genotype-treatment interactions, with genotypic effects evident in either only GC-treated or only control-treated conditions. Using a novel statistical framework, we identified interactions that influence the expression of 26 genes known to play central roles in GC-related pathways (e.g. NQO1, AIRE, and SGK1) and that influence the secretion of IL6. Public Library of Science 2011-07-07 /pmc/articles/PMC3131293/ /pubmed/21750684 http://dx.doi.org/10.1371/journal.pgen.1002162 Text en Maranville et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Maranville, Joseph C. Luca, Francesca Richards, Allison L. Wen, Xiaoquan Witonsky, David B. Baxter, Shaneen Stephens, Matthew Di Rienzo, Anna
spellingShingle	Maranville, Joseph C. Luca, Francesca Richards, Allison L. Wen, Xiaoquan Witonsky, David B. Baxter, Shaneen Stephens, Matthew Di Rienzo, Anna Interactions between Glucocorticoid Treatment and Cis-Regulatory Polymorphisms Contribute to Cellular Response Phenotypes
author_facet	Maranville, Joseph C. Luca, Francesca Richards, Allison L. Wen, Xiaoquan Witonsky, David B. Baxter, Shaneen Stephens, Matthew Di Rienzo, Anna
author_sort	Maranville, Joseph C.
title	Interactions between Glucocorticoid Treatment and Cis-Regulatory Polymorphisms Contribute to Cellular Response Phenotypes
title_short	Interactions between Glucocorticoid Treatment and Cis-Regulatory Polymorphisms Contribute to Cellular Response Phenotypes
title_full	Interactions between Glucocorticoid Treatment and Cis-Regulatory Polymorphisms Contribute to Cellular Response Phenotypes
title_fullStr	Interactions between Glucocorticoid Treatment and Cis-Regulatory Polymorphisms Contribute to Cellular Response Phenotypes
title_full_unstemmed	Interactions between Glucocorticoid Treatment and Cis-Regulatory Polymorphisms Contribute to Cellular Response Phenotypes
title_sort	interactions between glucocorticoid treatment and cis-regulatory polymorphisms contribute to cellular response phenotypes
description	Glucocorticoids (GCs) mediate physiological responses to environmental stress and are commonly used as pharmaceuticals. GCs act primarily through the GC receptor (GR, a transcription factor). Despite their clear biomedical importance, little is known about the genetic architecture of variation in GC response. Here we provide an initial assessment of variability in the cellular response to GC treatment by profiling gene expression and protein secretion in 114 EBV-transformed B lymphocytes of African and European ancestry. We found that genetic variation affects the response of nearby genes and exhibits distinctive patterns of genotype-treatment interactions, with genotypic effects evident in either only GC-treated or only control-treated conditions. Using a novel statistical framework, we identified interactions that influence the expression of 26 genes known to play central roles in GC-related pathways (e.g. NQO1, AIRE, and SGK1) and that influence the secretion of IL6.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131293/
_version_	1611464204864192512

Interactions between Glucocorticoid Treatment and Cis-Regulatory Polymorphisms Contribute to Cellular Response Phenotypes

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