The Role And Significance Of Vitamin D System In Neuromyelitis Optica Spectrum Disorder

Objective:To investigate the role and significance of the new polymorphic site of vitamin D receptor gene in neuromyelitis optica spectrum disorder(NMOSD)in low sunshine and low latitude region,and to find the susceptibility/protective SNPs site of NMOSD.Methods:A total of 83 NMOSD patients and 83 healthy controls enrolled from the Department of Neurology,The Affiliated Hospital of Guizhou Medical University,between March 2017 to September 2018 were recruited in the study.Polymerase chain reaction(PCR)and direct DNA sequencing were used to detect the mutations of vitamin D receptor(VDR)gene in NMOSD patients and healthy controls.Serum vitamin D levels were measured by electro-chemiluminescence immunoassay(ECLI).Results:There were two polymorphism sites were detected with VDR gene exon 10 in NONSD patients.And there was statistically significant difference in genotype and allele frequency of two sites between NMOSD patients and healthy controls(P<0.05).The risk of NMOSD were significantly increased while carrying mutation genotypes of these 2 SNPs(P<0.05).NMOSD patients with vitamin D low and carrying CA/GT genotype were significantly higher than healthy controls(P<0.05).There was no correlation between VDR gene polymorphisms and the EDSS scores.And there was no difference in relapses among NMOSD patients with different genotypes.NMOSD patients showed a significantly lower vitamin D level than healthy controls(P<0.05).Serum vitamin D levels of patients showed significantly inverse correlation with their EDSS scores,while serum vitamin D levels were positively correlated with the C3 in NMOSD patients.The relapses of NMOSD patients with vitamin D deficiency and insufficiency were significantly higher than vitamin D sufficiency group(P<0.05).Conclusion:(1)In this study,two new SNPs of VDR gene were found in NMOSD patients.The results not only complemented the NMOSD susceptibility gene mutation spectrum,but also helped to screen high-risk population of NMOSD.(2)the new polymorphic site of vitamin D receptor gene is associated with the susceptibility to NMOSD,and serum vitamin D levels were generally low in patients with the two polymorphic sites.It may be involved in the pathogenesis of disease by weakening the vitamin D/VDR signal transduction pathway.(3)The level of serum vitamin D in NMOSD patients is low,and is closely related to the severity of the disease and recurrence times.Serum vitamin D may be involved in the pathogenesis of NMOSD,and reflect the severity of the disease.Objective: To explore the role of vitamin D metabolism related genes in the pathogenesis of neuromyelitis optica spectrum disorders(NMOSD),and to provide new ideas for the treatment of NMOSD.Methods: We used electro-chemiluminescence immunoassay(ECLI)to detect serum vitamin D,and adopted real-time quantitative polymerase chain reaction(PCR)to detect the expression of vitamin D receptor(VDR),CYP24A1 and CYP27B1 in NMOSD patients and healthy controls.Results: We found significant lower levels of vitamin D in NMOSD patients compared with healthy controls(P=0.001),while the expression of VDR and CYP27B1 was significantly up-regulated compared with healthy controls(P<0.001;P=0.016).This study found that the expression of VDR,CYP27B1 and CYP24A1 were not related with gender,age,disease duration and AQP4-IgG in NMOSD patients(P > 0.05).Spearman correlation analysis showed that the expression of VDR and CYP27B1 was not related to expanded disability status scale(EDSS)score and relapses.Conclusion: Down-regulation of serum vitamin D levels and up-regulation of VDR and CYP27B1 is likely to happen in NMOSD patients.The changes of the CYP24A1 gene expression were not observed,which can be a statistic error caused by small sample.Consequently,our research suggested a possible role of vitamin D signaling pathways participating disease mechanism.But larger sample size was needed to fiirther analyze the vitamin D metabolism genes to verify current results.