LINE-1 Methylation Status in Multiple Sclerosis Patients Is Associated with Changes in Folate Metabolism.

Abstract

The disruption of epigenetic regulation and the development of abnormal DNA methylation patterns are crucial steps in the pathogenesis of neurodegenerative diseases. Methylation alterations in multiple sclerosis (MS) patients may contribute to the dysregulation of gene expression linked to the regulation of inflammation, myelin production, and the preservation of the integrity of the myelin sheath. The possibility that epigenetic alterations could be reversed provides a rationale for studying their mechanisms. In this study, we evaluated the methylation status of LINE-1 retrotransposons in the peripheral blood cells of patients with MS and healthy controls. In healthy individuals, LINE-1 methylation levels were observed to decrease with advancing age. MS patients exhibited a positive correlation between LINE-1 methylation and MS duration. The study indicates that the level of LINE-1 methylation is notably higher in progressive MS compared to the remitting type. LINE-1 methylation variations in MS patients were observed to be associated with the serum levels of homocysteine and vitamin B9, and dependent on the genotype for the C677T polymorphism of the MTHFR gene as well. The data obtained point to the contribution of the C677T polymorphism to the appearance of epigenetic disorders in MS development and suggest that hypermethylation may be mediated by disruptions in the folate metabolism that accompany MS.