DNA methylation-related vitamin D receptor low expression in multiple sclerosis

Multiple Sclerosis (MS) is a neurodegenerative autoimmune disease characterized by recurrent episodes of demyelination and axonal injury mediated primarily by CD4+ T-helper cells with a pro inflammatory Th1 phenotype, macrophages, and soluble mediators of inflammation. Calcitriol (1α, 25(OH)2-Vitamin D3) binds to the vitamin D receptor (VDR) andregulates differentiation of the immune cells, and may therefore be useful in the treatment of autoimmune diseases as animmunomoderator drug. Vitamin D3 clinically used to moderate patient's symptoms. But in some patients no clinicalimprovement had been observed any more. Nowadays, scientists' attention is focused on epigenetic alteration such as differences in CpG dinucleotide methylation of some disorders like Arthritis Rheumatoid, Lupus Erythematous, different type of cancers and so. VDR binds to Vit D3 and RXR (Retinoic acid receptor) and this heterodimer binds to VDRE (VDR Element) upstream of target genes. The aim of the study was to determine whether is the VDR promoter methylation cause of its low expression in those group that doesn't respond to Vit D3 therapy or not. So we used bisulfite converted DNA, which extracted from 15 cases of twogroups –which respond and doesn't respond to Vit D3- and converted by ZymoResearch bisulfite conversion kit, andspecific primers for three potential regions of the VDR CpG island to perform Methylation Specific High Resolution Melting analysis (MS-HRM). Our analysis shown different pattern between two groups. Further, our data confirmed by DNA sequencing

کلیدواژه ها:

Multiple Sclerosis ، Epigenetics ، promoter methylation ، Vitamin D Receptor