Epigenetics in Multiple Sclerosis

Multiple sclerosis (MS) is a common autoimmune disease of the central nervous system. Although the exact cause of MS is unknown, researchers agree that both genetic and environmental factors contribute to its development and progression. Recently, researchers discovered five novel MS risk genes in a German cohort that regulate epigenetic changes. Moreover, the researchers propose that there may be a potential role of epigenetics in multiple sclerosis disease development and progression.


Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system. It is characterized by the loss of myelin surrounding neurons, and clinically presents with fatigue, numbness, tingling, vision problems, bladder problems, and a lack of coordination, amongst other symptoms. The progression and severity of the disease varies greatly between individuals. Currently, treatment options are able to slow disease progression and control symptoms, but are not a permanent cure. Although, no underlying cause of MS has been discovered, current research suggests that both genetics and environmental factors play a significant role. To this end, several studies have demonstrated that multiple regions in the major histocompatibility complex (MHC) genes – which help the immune system recognize our cells as non-threatening – are associated with risk of MS. Additionally, there are regions outside of the MHC that have also been associated with an increased risk. Understanding the role of these genetic components and how they may contribute to the development of MS is crucial as it can lead to better care and more appropriate therapies.

To investigate how genetic variations can increase the risk of MS, researchers conducted a genome-wide association study on a German cohort consisting of 4,888 MS patients, and 10,935 individuals without MS (control). Their study confirmed the association between genetic variants in the MHC region and MS progression, as previously demonstrated by several research groups. In addition, they found fifteen regions outside the MHC that showed significant association with MS. Ten of the fifteen regions were already established in a previous study, and therefore not investigated further. The five remaining genetic variants discovered outside the MHC affected the genes DLEU1 (deleted in lymphocytic leukemia 1), SHMT1 (serine hydroxymethyltransferase), L3MBTl3 (Lethal (3) malignant brain tumour-like protein 3), ERG (transcription factor), and MAZ (transcription factor) genes.

The five risk genes discovered in the study play an important role in several regulatory processes of the immune system. Furthermore, they have important roles in epigenetic regulation (changes in gene function without altering DNA). Interestingly, previous studies demonstrate that epigenetic alterations including DNA methylation and histone modifications have been observed in tissues and cells of MS patients. This led to the idea that perhaps alterations of these genes leads to epigenetic changes, which in turn contribute to the development of MS. Furthermore, it is known that the environment significantly alters epigenetic status of our genetic information. Therefore, environmental conditions may influence expression of disease-associated genes and contribute to the progression of MS. Unfortunately, the exact mechanism of how epigenetic changes and MS susceptibility genes contribute to the development of MS remains unknown. Henceforth, further research is required in order to fully understand MS, and develop prevention and/or treatment approaches.




Written By: Haisam Shah, BSc

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