Abstract
IntroductionVitamin D has important roles as a natural immune modulator via regulating the expression of genes which have been implicated in the pathophysiology of autoimmune diseases. Vitamin D function and its deficiency have been linked to a wide range of metabolic disorders including disorders of calcium metabolism, malignant, cardiovascular, infectious, neuromuscular, and inflammatory diseases. Environmental factors, genetic factors, and epigenetic changes contribute to Behcet's disease (BD) development. The aim of our study was to analyze the expression level and methylation status of the vitamin D receptor (VDR) gene promoter in the peripheral blood mononuclear cells (PBMCs) of patients with BD.MethodsIn a case‐control study, 48 Iranian Azeri patients with BD and 60 age‐, sex‐ and ethnically‐matched healthy controls were included. Venous blood samples were collected and PBMCs were isolated by Ficoll protocol. The DNA and RNA were subsequently extracted. Promoter methylation levels were evaluated by MeDIP‐quantitative polymerase chain reaction (qPCR). The expression of VDR was evaluated by real‐time PCR.ResultsThe results of quantitative real‐time PCR analysis showed that the level of VDR expression in patients with BD was significantly lower than the control group (P = .013). There was no significant difference in the level of DNA methylation in the BD and control groups (P > .05). As the results show, the expression level of VDR gene was significantly different between female and male in the patient group (P = .001). VDR gene expression was significantly higher in subjects with phlebitis. No correlation was observed between VDR gene expression rate and BD activity.Conclusion VDR gene expression decreased in patients with BD. However, there is no suggestion evidence that the expression level of VDR is regulated by a unique DNA methylation mechanism. No correlation exists between VDR gene expression and BD activity.
Highlights
Vitamin D has important roles as a natural immune modulator via regulating the expression of genes which have been implicated in the pathophysiology of autoimmune diseases
vitamin D receptor (VDR) gene expression decreased in patients with Behcet's disease (BD)
There is no suggestion evidence that the expression level of VDR is regulated by a unique DNA methylation mechanism
Summary
Vitamin D has important roles as a natural immune modulator via regulating the expression of genes which have been implicated in the pathophysiology of autoimmune diseases. The aim of our study was to analyze the expression level and methylation status of the vitamin D receptor (VDR) gene promoter in the peripheral blood mononuclear cells (PBMCs) of patients with BD. Results: The results of quantitative real‐time PCR analysis showed that the level of VDR expression in patients with BD was significantly lower than the control group (P = .013). The expression level of VDR gene was significantly different between female and male in the patient group (P = .001). The genes involved in the regulation and synthesis of vitamin D include 25‐hydroxylase (CYP2R1), 1α‐hydroxylase (CYP27B1), 24‐hydroxylase (CYP24A1), and DHCR7.13-15 Vitamin D exists in two major physiologically forms: 25‐hydroxyvitamin D3 (25[OH] D3) that is obtained from UV irradiation and 1α, 25 dihydroxyvitamin D3 (1α, 25[OH] 2D3) that is synthesized in the skin. This form of Vitamin D is synthesized from 7‐dehydrocholesterol when exposed to UVB.[16]
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