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Updated: Jun 13, 2026
Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
No evidence for an effect of DNA methylation on multiple sclerosis severity at HLA-DRB1*15 or HLA-DRB5
Adam E Handel1, Gabriele C De Luca, Julia Morahan
1Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
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.
Insights
This study investigated DNA methylation in multiple sclerosis (MS) genetic factors HLA-DRB1*1501 and HLA-DRB5. Researchers found no significant impact of DNA methylation on MS disease severity or phenotypic heterogeneity.
Area of Science:
- Neuroimmunology
- Genetics
- Epigenetics
Background:
- Multiple sclerosis (MS) is a heterogeneous neurological disorder with significant genetic influence.
- Major histocompatibility complex (MHC) alleles, notably HLA-DRB1*1501, are key genetic determinants of MS susceptibility and clinical outcome.
- Interactions between HLA-DRB1*1501 and HLA-DRB5 are suggested to influence MS disease severity.
Purpose of the Study:
- To investigate the potential role of DNA methylation at HLA-DRB1*1501 and HLA-DRB5 in contributing to the phenotypic variability observed in multiple sclerosis.
- To assess epigenetic modifications as a factor in MS disease heterogeneity.
Main Methods:
- Utilized an extremes-of-outcome study design comparing patients with benign and malignant MS.
- Analyzed DNA methylation patterns specifically at the HLA-DRB1*1501 and HLA-DRB5 loci in 48 benign and 20 malignant MS patients.
Main Results:
- No statistically significant association was found between DNA methylation at HLA-DRB1*1501 and/or HLA-DRB5 and the severity of multiple sclerosis.
- The study did not identify DNA methylation as a significant contributor to MS phenotypic heterogeneity in the analyzed samples.
Conclusions:
- DNA methylation at HLA-DRB1*1501 and HLA-DRB5 does not appear to be a major determinant of MS disease severity or heterogeneity.
- Time- or tissue-specific epigenetic effects cannot be entirely excluded and warrant further investigation.
