The development of new genetic tools using next-generation sequencing: e.g., chromatin immunoprecipitation sequencing (ChIP-seq) and the accompanying rapid progress of epigenomics has made it possible to recognize that the association between vitamin D and MS could be based on the extensive and characteristic genomic binding of the vitamin D receptor (VDR).
Our results indicate that the distribution of investigated vitamin D receptor polymorphisms is a risk factor for multiple sclerosis susceptibility and progression in the Czech population.
The purpose of this study was to evaluate the association of VDR Apa-I, Bsm-I, Fok-I, Taq-I single nucleotide polymorphisms (SNPs) with multiple sclerosis (MS) risk in an Iranian Kurdish population.
An alternative promoter of the VDR gene shows altered DNA methylation levels in patients with multiple sclerosis, and it is associated with VDR mRNA upregulation.
Additionally, Asian or low latitude (20.1-30°N) people with ApaI homozygous genotype, '> 2013' publication year people in the allele contrast and dominant models of FokI, '> 40 years' age people with BsmI recessive model also indirectly significantly affected the association between VDR gene polymorphisms and MS risk.
The aim of this study was to investigate the expression levels of vitamin D receptor (VDR) and NF-κB mRNAs in vitamin D (VD) supplemented multiple sclerosis (MS) patients.
By logistic regression analysis, we revealed that genotype BB (AA) of BsmI VDR gene polymorphism is decreasing the risk of MS (BB (AA) vs Bb (AG) + bb (GG); OR = 0.59, 95% CI = 0.39-0.90, plog = 0.014).
Finally, CYP24A1 was highly induced by the active form of vitamin D and its expression correlated with the expression of VDR in LCLs but neither the MS-associated variant in the region (rs2248359) nor any other variant located in 1 Mb around CYP24A1 was associated with its expression.
VDR polymorphisms seem to have a notable connection with MS pathogenesis, however, study of more big population and functional work on the gene structure and its function are recommended.
The distribution of genotype and allele frequencies of the four VDR polymorphisms did not differ significantly between MS patients and healthy controls, and were unrelated to the forms and the course of MS. Low serum levels of 25(OH)D were observed in MS patients but no association was observed between VDR and 25(OH)D levels except for Fok-I.
Since vitamin D acts through the vitamin D receptor (VDR), association of single nucleotide polymorphisms (SNPs) in the VDR gene might account for variations in the MS risk within populations.
However, to find the definite connection between genetic variations in VDR gene and MS disease in a population of South East of Iran, more researches on gene structure and its function with regard to patients' conditions are required.
The role of VDR gene polymorphism should be further studied in other large populations, and the distribution of other polymorphism, such as FokI and BsmI, should be also analysed to confirm another susceptibility polymorphisms gene for MS and to obtain more adequate strategies for treatment of MS.
Furthermore, MS susceptibility regions are preferentially targeted by both EBNA2 and VDR than by EBNA2 alone (enrichment difference = 1.722-fold, p = 0.0267).
Several studies have reported that genetic variations of VDR might be a risk factor for the development of autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), psoriasis, and autoimmune thyroid diseases (AITD).