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

J Neuroimmunol. 2016 Oct 15:299:84-89. doi: 10.1016/j.jneuroim.2016.08.019. Epub 2016 Sep 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD / genetics
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Cohort Studies
  • Disease Progression*
  • Female
  • Haplotypes / genetics*
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / pathology*
  • Receptors, Cell Surface / genetics
  • Receptors, Glucocorticoid / genetics*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Receptors, Cell Surface
  • Receptors, Glucocorticoid