Evidence for association of STAT4 and IL12RB2 variants with Myasthenia gravis susceptibility: What is the effect on gene expression in thymus?

J Neuroimmunol. 2018 Jun 15:319:93-99. doi: 10.1016/j.jneuroim.2018.03.008. Epub 2018 Mar 17.

Abstract

Myasthenia gravis (MG) is an autoimmune disease mediated by the presence of autoantibodies that bind mainly to the acetylcholine receptor (AChR) in the neuromuscular junction. In our case-control association study, we analyzed common variants located in genes of the IL12/STAT4 and IL10/STAT3 signaling pathways. A total of 175 sporadic MG patients of Greek descent, positively detected with anti-AChR autoantibodies and 84 ethnically-matched, healthy volunteers were enrolled in the study. Thymus samples were obtained from 16 non-MG individuals for relative gene expression analysis. The strongest signals of association were observed in the cases of rs6679356 between the late-onset MG patients and controls and rs7574865 between early-onset MG and controls. Our investigation of the correlation between the MG-associated variants and the expression levels of each gene in thymus did not result in significant differences.

Keywords: Genetic association study; IL12RB2; JAK2; Myasthenia gravis; STAT3; STAT4; TYK2; Thymus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Female
  • Gene Expression / genetics
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Greece
  • Humans
  • Male
  • Middle Aged
  • Myasthenia Gravis / genetics*
  • Myasthenia Gravis / immunology
  • Polymorphism, Single Nucleotide
  • Receptors, Interleukin-12 / genetics*
  • STAT4 Transcription Factor / genetics*
  • Thymus Gland* / immunology

Substances

  • IL12RB2 protein, human
  • Receptors, Interleukin-12
  • STAT4 Transcription Factor
  • STAT4 protein, human