title: 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.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Adam E
authors.initials: AE
authors.lastname: Handel
authors.forename: Gabriele C
authors.initials: GC
authors.lastname: De Luca
authors.forename: Julia
authors.initials: J
authors.lastname: Morahan
authors.forename: Lahiru
authors.initials: L
authors.lastname: Handunnetthi
authors.forename: A Dessa
authors.initials: AD
authors.lastname: Sadovnick
authors.forename: George C
authors.initials: GC
authors.lastname: Ebers
authors.forename: Sreeram V
authors.initials: SV
authors.lastname: Ramagopalan
mesh_terms: D000483:Alleles; D015331:Cohort Studies; D018899:CpG Islands / Q000276:immunology; D019175:DNA Methylation / Q000276:immunology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics* / Q000378:metabolism; D059811:HLA-DRB1 Chains; D059847:HLA-DRB5 Chains; D006801:Humans; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: C408982:CPG-oligonucleotide; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen; D059847:HLA-DRB5 Chains; D009838:Oligodeoxyribonucleotides