Glucocorticoid receptor haplotypes conferring increased sensitivity (BclI and N363S) are associated with faster progression of multiple sclerosis

Jeroen Melief; Jan W. Koper; Erik Endert; Holger J. Møller; Jörg Hamann; Bernard M. Uitdehaag; Inge Huitinga; Holger J. Moller; Jorg Hamann

doi:https://doi.org/10.1016/j.jneuroim.2016.08.019

Glucocorticoid receptor haplotypes conferring increased sensitivity (BclI and N363S) are associated with faster progression of multiple sclerosis

Jeroen Melief, Jan W. Koper, Erik Endert, Holger J. Møller, Jörg Hamann, Bernard M. Uitdehaag, Inge Huitinga, Holger J. Moller, Jorg Hamann

Research output: Contribution to journal › Article › Academic › peer-review

12 Citations (Scopus)

Abstract

As high cortisol levels are implicated in suppressed disease activity of multiple sclerosis (MS), glucocorticoid receptor (GR) polymorphisms that affect glucocorticoid (GC) sensitivity may impact on this by changing local immunomodulation or regulation of the hypothalamus-pituitary-adrenal (HPA)-axis. In this post-mortem study, we investigated whether GR haplotypes affect MS disease course and production of cortisol and soluble CD163 (sCD163), a molecule induced by GC on microglia/macrophages. We found that GR haplotypes that confer high GC sensitivity are associated with more aggressive MS but do not affect levels of cortisol secreted by the HPA-axis or shedding of CD163

Original language	English
Pages (from-to)	84-89
Journal	Journal of Neuroimmunology
Volume	299
DOIs	https://doi.org/10.1016/j.jneuroim.2016.08.019
Publication status	Published - 15 Oct 2016

Keywords

Cortisol
Glucocorticoid receptor polymorphisms
Multiple sclerosis
Soluble CD163

Access to Document

https://doi.org/10.1016/j.jneuroim.2016.08.019

Cite this

@article{9ea896655c554923b43d3c136c2a4aa1,

title = "Glucocorticoid receptor haplotypes conferring increased sensitivity (BclI and N363S) are associated with faster progression of multiple sclerosis",

abstract = "As high cortisol levels are implicated in suppressed disease activity of multiple sclerosis (MS), glucocorticoid receptor (GR) polymorphisms that affect glucocorticoid (GC) sensitivity may impact on this by changing local immunomodulation or regulation of the hypothalamus-pituitary-adrenal (HPA)-axis. In this post-mortem study, we investigated whether GR haplotypes affect MS disease course and production of cortisol and soluble CD163 (sCD163), a molecule induced by GC on microglia/macrophages. We found that GR haplotypes that confer high GC sensitivity are associated with more aggressive MS but do not affect levels of cortisol secreted by the HPA-axis or shedding of CD163",

keywords = "Cortisol, Glucocorticoid receptor polymorphisms, Multiple sclerosis, Soluble CD163",

author = "Jeroen Melief and Koper, {Jan W.} and Erik Endert and M{\o}ller, {Holger J.} and J{\"o}rg Hamann and Uitdehaag, {Bernard M.} and Inge Huitinga and Moller, {Holger J.} and Jorg Hamann",

year = "2016",

month = oct,

day = "15",

doi = "https://doi.org/10.1016/j.jneuroim.2016.08.019",

language = "English",

volume = "299",

pages = "84--89",

journal = "Journal of Neuroimmunology",

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TY - JOUR

T1 - Glucocorticoid receptor haplotypes conferring increased sensitivity (BclI and N363S) are associated with faster progression of multiple sclerosis

AU - Melief, Jeroen

AU - Koper, Jan W.

AU - Endert, Erik

AU - Møller, Holger J.

AU - Hamann, Jörg

AU - Uitdehaag, Bernard M.

AU - Huitinga, Inge

AU - Moller, Holger J.

AU - Hamann, Jorg

PY - 2016/10/15

Y1 - 2016/10/15

N2 - As high cortisol levels are implicated in suppressed disease activity of multiple sclerosis (MS), glucocorticoid receptor (GR) polymorphisms that affect glucocorticoid (GC) sensitivity may impact on this by changing local immunomodulation or regulation of the hypothalamus-pituitary-adrenal (HPA)-axis. In this post-mortem study, we investigated whether GR haplotypes affect MS disease course and production of cortisol and soluble CD163 (sCD163), a molecule induced by GC on microglia/macrophages. We found that GR haplotypes that confer high GC sensitivity are associated with more aggressive MS but do not affect levels of cortisol secreted by the HPA-axis or shedding of CD163

AB - As high cortisol levels are implicated in suppressed disease activity of multiple sclerosis (MS), glucocorticoid receptor (GR) polymorphisms that affect glucocorticoid (GC) sensitivity may impact on this by changing local immunomodulation or regulation of the hypothalamus-pituitary-adrenal (HPA)-axis. In this post-mortem study, we investigated whether GR haplotypes affect MS disease course and production of cortisol and soluble CD163 (sCD163), a molecule induced by GC on microglia/macrophages. We found that GR haplotypes that confer high GC sensitivity are associated with more aggressive MS but do not affect levels of cortisol secreted by the HPA-axis or shedding of CD163

KW - Cortisol

KW - Glucocorticoid receptor polymorphisms

KW - Multiple sclerosis

KW - Soluble CD163

U2 - https://doi.org/10.1016/j.jneuroim.2016.08.019

DO - https://doi.org/10.1016/j.jneuroim.2016.08.019

M3 - Article

C2 - 27725129

SN - 0165-5728

VL - 299

SP - 84

EP - 89

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

ER -