Investigation of the NF-KB signaling pathway in whole blood samples of patients with Multiple Sclerosis

The present research is on the signaling pathways of NFKB, on nearly 200 DNA blood samples of the patients with Multiple Sclerosis (MS), focused on a set of genetic and epigenetic alterations on promoters of that genes, using PCR-RFLP, sequencing, andmethylation-specific PCR. Autoimmune MS disease is characterized by demyelination due to immune reactions against the myelin sheath, and NF-KB is an inducible transcription factor in lymphocytes and the immune system, presents in the cytoplasm in association with inhibitory proteins (IkB), involved in the regulation of major inflammatory responses. NF-kB signaling pathways are initiated through extracellular stimuli and following activation of the IκB kinase (IKK) complex, signal leads to the degradation of IkB and the resultant release and translocation of the relevant NF-kB into the nucleus for transcriptional activation. Most of MS patients had relapsing/remitting status and healthy control individuals matched based on sex and age. The results of these studies revealed there are no significant differences in the frequency of the -94 ins/del ATTG polymorphism in the promoter of NF-KB gene but the genotype frequency of IkBα -881 A/G was significantly higher in the MS patients than in the controls. Methylation pattern of IKK gene promoter was also significantly correlated with the disease susceptibility. The role of NF-kB in autoimmune diseases is undeniable and the association between IkB promoter gene polymorphisms/ hyper-methylation of related IKK promoter gene and susceptibility of MS disease are partly due to different transcriptional activities and the activation of NF-kB.

Keywords:

Multiple sclerosis , Transcription factor , NFKB , Polymorphism , Epigenetic