DNA Methylation in Multiple Sclerosis

Multiple Sclerosis (MS) is a leading cause of lifelong disability in young adults. The disease strikes individuals in their most productive years with incurable and progressive course that results in development of fatigue and accumulation of physical and cognitive disability. MS is characterized by autoimmune destruction of the myelin and subsequent neurodegeneration. This chronic disease of the central nervous system is likely triggered by environmental factors such as smoking, lack of sun exposure/vitamin D deficiency and infection, in genetically predisposed individuals, the strongest influence coming from HLA-DRB1 variants within the HLA class II locus. However, the mechanisms underlying susceptibility to MS are still puzzling and specific clinical translations are lacking. Emerging evidence suggests the implication of epigenetic mechanisms such as DNA methylation in the pathogenesis of MS. In this chapter, we aimed to review findings from DNA methylation studies in MS and discuss their clinical relevance. We first present a critical overview of the outcomes of DNA methylation studies in immune cells and brain tissue from MS patients. We then discuss emerging evidence supporting a role of DNA methylation in mediating the effect from the major genetic risk variant HLA-DRB1*15:01 and environmental risk factors, smoking and vitamin D deficiency, in MS. We also describe the potential of DNA methylation-based biomarkers and therapies for precision medicine in MS. We expect that the encouraging findings from DNA methylation studies in MS might open new avenues for a better understanding and treatment MS patients.