Changes in Deoxyribonucleic Acid Methylation Contribute to the Pathophysiology of Multiple Sclerosis.

Naiara Celarain,Jordi Tomas-Roig

doi:10.3389/fgene.2019.01138

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by loss of coordination, weakness, dysfunctions in bladder capacity, bowel movement, and cognitive impairment. Thus, the disease leads to a significant socioeconomic burden. In the pathophysiology of the disease, both genetic and environmental risk factors are involved. Gene x environment interaction is modulated by epigenetic mechanisms. Epigenetics refers to a sophisticated system that regulates gene expression with no changes in the DNA sequence. The most studied epigenetic mechanism is the DNA methylation. In this review, we summarize the data available from the current literature by grouping sets of differentially methylated genes in distinct biological categories: the immune system including innate and adaptive response, the DNA damage, and the central nervous system.

Highlights

Multiple sclerosis (MS) is a potentially disabling central nervous system (CNS) disease characterized by inflammation, demyelination, and axonal degeneration
The findings reported by Chomyk et al (2017) and Kulakova et al (2016) suggest that a substantial number of DNA methylation (DNAme) to Immunoglobulin superfamily member 9B (IGSF9B) could be accompanied by lower transcription rates as well as a selective loss of GABAergic interneurons (Gil-Varea et al, 2018)
Multiple sclerosis is a chronic inflammatory CNS disease originating from a complex interaction between genes and the environment

Summary

Introduction

Multiple sclerosis (MS) is a potentially disabling central nervous system (CNS) disease characterized by inflammation, demyelination, and axonal degeneration. In line with these findings, lower DNAme levels for AHRR have been measured in demyelinated hippocampi (Chomyk et al, 2017), CD4+ T cells (Graves et al, 2014), and PBMCs (Marabita et al, 2017) of MS patients. In line with these findings, elevated levels of DNAme for RUNX3 and CDKN2A were found in MS patients compared to controls (Liggett et al, 2010; Sokratous et al, 2018).

Results

Conclusion