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.
authors.affiliation: Department of Neuroimmunology, Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Melief
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Koper
authors.affiliation: Department of Clinical Chemistry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Endert
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Holger J
authors.initials: HJ
authors.lastname: Møller
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hamann
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Bernard M
authors.initials: BM
authors.lastname: Uitdehaag
authors.affiliation: Department of Neuroimmunology, Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands. Electronic address: i.huitinga@nin.knaw.nl.
authors.forename: Inge
authors.initials: I
authors.lastname: Huitinga
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; D011965:Receptors, Glucocorticoid
keywords: Cortisol; Glucocorticoid receptor polymorphisms; Multiple sclerosis; Soluble CD163