Abstract Details

Title Analysis of the Methylome in Multiple Sclerosis Patients from an Underrepresented Minority Population

Topic Multiple Sclerosis

Presentation(s) P3 - Poster Session 3 (12:00 PM-1:00 PM)

Poster/Presentation
Number 9-015

Objective Differential methylation of genomic DNA (gDNA) was analyzed in samples obtained from multiple sclerosis patients and control donors.

Background African American patients frequently develop earlier onset of MS and a more severe disease course that can be resistant to disease modifying treatments. Prior work from our group demonstrated differential expression of RNA splice variants in immune cells from MS patients as compared to control donors.

Design/Methods Blood samples were obtained from patients with MS and healthy controls under an IRB-approved protocol (UIC Neuroimmunology Biobank). gDNA was purified from whole blood. Infinium MethylationEPIC bead arrays were utilized to characterize gDNA methylation. Acquisition and analysis of data were performed at the Roy J. Carver Biotechnology Center at the University of Illinois, Urbana-Champaign. Data were normalized and filtered with the minfi R package (Aryee et al., 2014). Probes were removed from analysis for low detection value, sex differences, CpG sites with known SNP's, probe cross-reactivity, and detectable effects of specific disease modifying treatments for MS. The effects of race were filtered for the disease state comparison (all MS versus all control donors).

Results Approximately 63% of donors were African American (10/16 samples). Data revealed marked differences between racial groups. In addition, differential methylation within HLA-DRB1 was observed at 14 CpG sites previously identified as biomarkers (Kular et al., 2018). Novel findings for the MS versus control comparison included identification of differentially methylated regions in genes that encode regulators of alternative RNA splicing. In the AA MS versus AA control sub-group, differential methylation was observed in these same regions and in a gene cluster involved in synaptic regulation.

Conclusions Differential methylation analysis of gDNA reveals potentially novel mechanisms to regulate alternative RNA splicing and neuronal function in MS patients. These biomarkers may be of particular relevance in the regulation of disease susceptibility and severity in African American patients.

Authors/Disclosures
Neda Sattarnezhad Oskouei, MD (Stanford Univesrity) PRESENTER	Dr. Sattarnezhad Oskouei has received research support from National Institutes of Health (NIH). Dr. Sattarnezhad Oskouei has received research support from National Institute of Allergy and Infectious Diseases (NIAID).
Jeremy M. Bingen (University of Illinois at Chicago)	Mr. Bingen has nothing to disclose.
	No disclosure on file
Michael Carrithers, MD, PhD (University of Illinois College of Medicine)	The institution of Dr. Carrithers has received research support from Biogen.

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