No evidence for an effect of DNA methylation on multiple sclerosis severity at HLA-DRB1*15 or HLA-DRB5

J Neuroimmunol. 2010 Jun;223(1-2):120-3. doi: 10.1016/j.jneuroim.2010.03.002. Epub 2010 Apr 14.

Abstract

Multiple sclerosis (MS) is a complex neurological disease with huge variability in disease outcome. The majority of MS genetic susceptibility is determined by major histocompatibility complex (MHC) alleles, in particular haplotypes carrying HLA-DRB1*1501. HLA-DRB1*1501 also affects the clinical outcome of the disease and animal research has suggested that HLA-DRB5 interacts with HLA-DRB1*1501 to influence disease severity. We used an extremes-of-outcome design with 48 benign and 20 malignant MS patients to assess whether or not DNA methylation at HLA-DRB1*1501 and/or HLA-DRB5 also contributes to MS phenotypic heterogeneity. We found no significant effect of DNA methylation across HLA-DRB1*1501 and HLA-DRB5 on severity, although we cannot rule out time- or tissue-specific effects of DNA methylation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Cohort Studies
  • CpG Islands / immunology
  • DNA Methylation / immunology*
  • Genetic Predisposition to Disease / genetics
  • HLA-DR Antigens / genetics*
  • HLA-DR Antigens / metabolism
  • HLA-DRB1 Chains
  • HLA-DRB5 Chains
  • Humans
  • Middle Aged
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Oligodeoxyribonucleotides / genetics
  • Oligodeoxyribonucleotides / metabolism
  • Severity of Illness Index*

Substances

  • CPG-oligonucleotide
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HLA-DRB1*15 antigen
  • HLA-DRB5 Chains
  • Oligodeoxyribonucleotides