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.
An overrepresentation of the b allele of the vitamin D receptor (VDR) has been detected in autoimmune diseases as type-1-diabetes and multiple sclerosis.
We analyzed SNPs within the VDR gene in association with the HLA-DRB1 locus in 641 MS patients diagnosed according to McDonald criteria and 558 age- and sex-matched healthy controls, to verify possible correlations between the vitamin D/VDR complex, HLA-DRB1, and susceptibility to MS.
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.
Vitamin D and its analogues inhibited experimental autoimmune encephalomyelitis (EAE, an animal model of MS) and there have been reports of small clinical trials on the treatment of MS with vitamin D. Furthermore, there have been discussions on the association between vitamin D levels and MS and about the genetic risk of vitamin D receptor (VDR) gene polymorphisms in MS.
Also, a recent study in twins with MS supports the notion that vitamin D levels are under regulation by genetic variation in the 1alpha-hydroxylase and vitamin D receptor genes, perhaps pointing to their importance in the disease pathogenesis.
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).
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.
Polymorphisms of the VDR have major effects on vitamin D function and metabolism, and some VDR genotypes have been linked to osteoporosis and MS. Because the safety of high doses of vitamin D has not been established yet, vitamin D hasn't been used in enough doses to increase the serum level to a desired therapeutic target.
This collective review focuses on three major factors that influence the incidences of multiple sclerosis (MS) to include ultraviolet radiation (UVR), vitamin D3 supplementation, and vitamin D receptor gene (VDRG) polymorphisms.
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.
In 512 patients with MS duration of 10 or more years, we studied the association of VDR single nucleotide polymorphisms (A/G(1229), C/G(3444), G/A(3944), CC(20965), CC(30056), F/f(30875), C/T(48200), T/t(65013)) with outcome or disability. ff(30875) frequency was lower in cases with EDSS > or = 6.0 than with scores < 6.0 (odds ratio = 0.38, 95% CI = 0.20-0.70).
In 512 patients with MS duration of 10 or more years, we studied the association of VDR single nucleotide polymorphisms (A/G(1229), C/G(3444), G/A(3944), CC(20965), CC(30056), F/f(30875), C/T(48200), T/t(65013)) with outcome or disability. ff(30875) frequency was lower in cases with EDSS > or = 6.0 than with scores < 6.0 (odds ratio = 0.38, 95% CI = 0.20-0.70).
However, the VDR Fok1 variant (rs2228570), selected for previously positive associations with MS susceptibility and 25(OH)D levels in MS patients showed marginally distorted transmission in DRB15-negative patients (p=0.03).
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.
Increased VDR expression in MS NAWM and inflammatory cytokine-induced amplified expression of VDR and CYP27B1 in chronic active MS lesions suggest increased sensitivity to vitamin D in NAWM and a possible endogenous role for vitamin D metabolism in the suppression of active MS lesions.
In this review we, discuss five major areas in vitamin D biology of high immunological significance: (1) the metabolism of vitamin D; (2) the significance of vitamin D receptor polymorphisms in autoimmune diseases, such as multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus; (3) vitamin D receptor transcriptional regulation of immune cell lineages, including Th1, Th17, Th2, regulatory T, and natural killer T cells; (4) the prevalence of vitamin D insufficiency/deficiency in patients with multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus; and finally, (5) the therapeutic effects of vitamin D supplementation on disease severity and progression.