Study On The Relation Between Serum Vitamin D Level,Vitamin D Metabolism-Related Gene And Pediatric Anti-Myelin Oligodendrocyte Glycoprotein Antibodies Associated Disorders

ObjectiveThe study aimed to analysis the clinical characteristics of patients with MOG Abs-positive,who had been diagnosed as acquired demyelination syndromes(ADSS).Then we investigated the correlation between vitamin D levels and ADSS.Numbers of SNP(single nucleotide polymorphisms)loci of gene related to vitamin D metabolism were selected to probe into the correlation between the SNP of vitamin D metabolism related gene and ADSS.Methods1.Clinical characteristics of MOG antibody associated disease(MOGAD)in pediatric patients with ADSSA total of 31 patients with MOG Abs-positive and 24 patients with MOG Abs-negative,who had been diagnosed as ADSS was enrolled from the Department of Neurology of Tianjin Children’s Hospital from 2017 to 2020.The basic details,symptoms,laboratory examination,MRI,EEG and neuroelectrophysiological data of the enrolled patients were summarized and analyzed,and the difference in clinical characteristics of patients with MOG Abs-positive and-negative was statistically analyzed by SPSS24.0.2.Analysis on the correlation between the level of serum 25-hydroxy vitamin D(25-(OH)D)and ADSS in childrenThe serum samples of enrolled patients and healthy controls were collected and the25-(OH)D was quantified by LC-MS/MS.The differences of 25-(OH)D between patients and heathy controls was analyzed.Then the difference of clinical characteristics between patients with normal level of 25-(OH)D and patients with deficient level was analyzed.The correlation between the deficiency of 25-(OH)D and ADSS was analyzed by binary Logistic regression.3.The correlation between SNP loci of vitamin D metabolism related genes and ADSS in childrenWe extracted the DNA samples from the peripheral blood of patients and heathy controls,and selected five SNP loci from five vitamin D metabolism related genes,rs12785878 of NADSYN1 gene,rs12794714 of CYP2R1 gene,rs7041 of GC gene,rs1544410 of VDR gene,rs17216707 of CYP24A1 gene.The relevant DNA fragments were amplified by PCR,and the genotyping was analyzed by the Sanger sequencing,high resolution dissolve curve.The statistical differences of genotype and allele distribution of SNP loci between patients and heathy controls were analyzed and the risk factors related to ADSS were screened out among the 5 selected SNP loci related to vitamin D metabolism gene.Results1.Clinical characteristics of MOG antibody associated disease(MOGAD)in pediatric patients with ADSSThe mean age of patients with MOG Abs-positive and-negative was 7.63±3.28 and8.06±3.94 respectively.In muscle tone,the number of patients with MOG Abs-positive was 3(25.00%),and the number of patients with MOG Abs-negative group was 12(38.71%),and the difference between the two groups was statistically significant(P=0.030).In the analysis of MRI characteristics,there were 4 cases of patients with MOG Abs-positive involved in the optic nerve lesion,accounting for16.67%,and no case of MOG Abs-negative patients was involved,showing a statistical difference between the two groups(P=0.031).2.Analysis on the correlation between the level of serum 25-hydroxy vitamin D(25-(OH)D)and ADSS in childrenThe mean value of 25-(OH)D in patients was 13.56±4.09ng/ml and the mean value in heathy controls was 27.46±7.81ng/ml,there was statistical difference between the groups(P=0.001).Among patients with normal and deficient level of 25-(OH)D,the ratio of males to females was similar,while the mean age of patients with normal and deficient level of 25-(OH)D was 9.03±3.15 ng/ml and 5.72±3.84 ng/ml,indicating significant difference between the two groups(P=0.0007).Among the clinical characteristics,there were significant differences in terms of reduced muscle strength,epileptic seizures between patients with normal and deficient level of 25-(OH)D(P <0.05).The correlation between gender,age,the level of 25-(OH)D and ADSS was analyzed by binary Logistic regression.After adjusting for confounding factors such as gender and age,the correlation between the level of 25-(OH)D and ADSS was significant,P<0.05,OR value was 0.921,95%confidence interval was 0.870 to0.975.3.The correlation between SNP loci of vitamin D metabolism related genes and ADSS in children Among the five SNP locis of vitamin D metabolism-related genes,there were three genotypes and two alleles at rs12785878 of NADSYN1 gene,rs12794714 of CYP2R1gene and rs7041 of GC gene.There are two genotypes and two alleles in rs1544410of VDR gene and rs17216707 of CYP24A1 gene.The distribution of genotype and allele in rs12785878 of NADSYN1 gene,rs12794714 of CYP2R1 gene and rs7041 of GC gene were statistically different between the two groups,P<0.05.The G allele at rs12785878 of NADSYN1 gene may be a risk factor for ADSS with MOG-Abs(OR=2.728,95%CI=[1.334-5.577]),the C allele at rs12794714 of CYP2R1 gene may be a risk factor for ADSS without MOG-Ab(OR=2.700,95%CI=[1.415-5.152])and the T allele at rs7041 of GC gene may be a risk factor for ADSS with MOG-Abs(OR=4.416,95%CI=[1.616-12.068]).There was no statistical difference in genotype and allele distribution in rs1544410 of VDR gene and rs17216707 of CYP24A1 gene.ConclusionThis study found that the enrolled patients with MOG Abs-positive and-negative had different clinical characteristics,so were Patients with normal and deficient level of vitamin D.The 25-(OH)D was correlated with the occurrence of ADSS.In the five selected vitamin D metabolism related genes,the G allele at rs12785878 of NADSYN1 gene and the T allele at rs7041 of GC gene may be a risk factor for ADSS with MOG-Abs,the C allele at rs12794714 of CYP2R1 gene may be a risk factor for ADSS without MOG-Abs.