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

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.

• Authors: Adam E Handel, Gabriele C De Luca, Julia Morahan, Lahiru Handunnetthi, A Dessa Sadovnick, George C Ebers, Sreeram V Ramagopalan
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 223 Issue 1-2 Pg. 120-3 (Jun 2010) ISSN: 1872-8421 [Electronic] Netherlands
• PMID: 20394989 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier B.V. All rights reserved.

Chemical References

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

Topics

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