Abstract
Objective Interferons (IFNs)-inducible myxovirus resistance protein A (MxA) has recently been used as an indirect marker of neutralizing antibody against IFN in patients with multiple sclerosis (MS). On the other hand, MxA inhibits the replication of viruses by means of modifying cellular function, including apoptotic pathway. Our objective is to investigate the genetic and pathological role of MxA in patients with MS. Methods We examined SNPs of MxA promoter region in 67 patients with MS. Moreover, to elucidate the functional roles of SNPs, we conducted Luciferase assay with pGL3-basic vector including patient-derived or artificially mutated MxA promoter region. Results A significantly higher frequency of the haplotype with − 88T and − 123A, which correlates with over-expression of MxA, was observed in MS. Moreover, we elucidated novel findings showing that nt − 88 played a leading part with type I IFNs and that nt − 123 played the same role independently without type I IFNs, respectively. Conclusion SNPs on MxA promoter region may play an important role in the pathophysiology of MS and provide a novel strategy for the therapeutic resolutions of MS.
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