scholarly journals Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Catia Pilon ◽  
Andrea Rebellato ◽  
Riccardo Urbanet ◽  
Vincenza Guzzardo ◽  
Rocco Cappellesso ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Methylation Status ◽  
Rare Event ◽  
Gene Promoter ◽  
Benign Tumors ◽  
Cancer Type ◽  
Adrenocortical Tumor ◽  
Vdr Gene

We previously showed a decreased expression of vitamin D receptor (VDR) mRNA/protein in a small group of adrenocortical carcinoma (ACC) tissues, suggesting the loss of a protective role of VDR against malignant cell growth in this cancer type. Downregulation of VDR gene expression may result from epigenetics events, that is, methylation of cytosine nucleotide of CpG islands in VDR gene promoter. We analyzed methylation of CpG sites in the VDR gene promoter in normal adrenals and adrenocortical tumor samples. Methylation of CpG-rich 5′ regions was assessed by bisulfite sequencing PCR using bisulfite-treated DNA from archival microdissected paraffin-embedded adrenocortical tissues. Three normal adrenals and 23 various adrenocortical tumor samples (15 adenomas and 8 carcinomas) were studied. Methylation in the promoter region of VDR gene was found in 3/8 ACCs, while no VDR gene methylation was observed in normal adrenals and adrenocortical adenomas. VDR mRNA and protein levels were lower in ACCs than in benign tumors, and VDR immunostaining was weak or negative in ACCs, including all 3 methylated tissue samples. The association between VDR gene promoter methylation and reduced VDR gene expression is not a rare event in ACC, suggesting that VDR epigenetic inactivation may have a role in adrenocortical carcinogenesis.

Functional characterization of WT1 binding sites within the human vitamin D receptor gene promoter

2001 ◽  
Vol 7 (2) ◽  
pp. 187-200 ◽  
Author(s):  
TAE HO LEE ◽  
JERRY PELLETIER
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Transcription Factor ◽  
Vitamin D Receptor ◽  
Binding Sites ◽  
Wilms Tumor ◽  
Cdna Array ◽  
Transcriptional Level ◽  
Vdr Gene ◽  
Downstream Target

The Wilms’ tumor suppressor gene, wt1, encodes a zinc finger transcription factor that can regulate gene expression. It plays an essential role in tumorigenesis, kidney differentiation, and urogenital development. To identify WT1 downstream targets, gene expression profiling was conducted using a cDNA array hybridization approach. We confirm herein that the human vitamin D receptor (VDR), a ligand-activated transcription factor, is a WT1 downstream target. Nuclear run on experiments demonstrated that the effect of WT1 on VDR expression is at the transcriptional level. Transient transfection assays, deletion mutagenesis, electrophoretic mobility shift assays, and chromatin immunoprecipitation assays suggest that, although WT1 is presented with a possibility of three binding sites within the VDR promoter, activation of the human VDR gene appears to occur through a single site. This site differs from a previously identified WT1-responsive site in the murine VDR promoter (Maurer U, Jehan F, Englert C, Hübinger G, Weidmann E, DeLucas HF, and Bergmann L. J Biol Chem 276: 3727–3732, 2001). We also show that the products of a Denys-Drash syndrome allele of wt1 inhibit WT1-mediated transactivation of the human VDR promoter. Our results indicate that the human VDR gene is a downstream target of WT1 and may be regulated differently than its murine counterpart.

scholarly journals Immunological analysis of vitamin D receptor gene expression in Egyptian patients with rheumatoid arthritis: relation to disease activity and functional disability

2020 ◽  
Vol 47 (1) ◽  
Author(s):  
Nevine Mohannad ◽  
Eman Saad Nassar ◽  
Mai Moaaz ◽  
Rehab Elnemr ◽  
Eman Anwar Sultan
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Vitamin D ◽  
Disease Activity ◽  
Vitamin D Receptor ◽  
Functional Disability ◽  
Receptor Gene ◽  
Roc Curve Analysis ◽  
Vdr Gene ◽  
Egyptian Patients

Abstract Background Vitamin D (vit D) deficiency has recently been associated with risk of development of rheumatoid arthritis (RA). The aim of this research was to assess vitamin D receptor (VDR) gene expression in Egyptian patients with RA and its relation with the inflammatory state, disease activity, and functional disability. Results RA patients had significantly lower vit D level and VDR gene expression compared to controls (mean ± 17.0 ± 6.65, 20.73 ± 8.42 ng/ml, p < 0.05 and 3.29 ± 5.47, 14.22 ± 12.60, p < 0.001 respectively). Receiver operating characteristic (ROC) curve analysis for VDR gene expression in RA patients revealed (area under the curve 0.826, cutoff value for low VDR expression 1.05 ng/ml). Patients with low VDR expression had significantly higher ESR, CRP, double positive RF+ anti-CCP+, DAS28, and MHAQ (p < 0.001, p = 0.001, p < 0.05, p < 0.001, p < 0.001) respectively. Conclusion Vitamin D and VDR expression are significantly lower in RA patients than controls. Patients with low VDR gene expression had significantly higher disease activity and disability. This may suggest that apart from low vit D levels, low VDR expression is associated with inflammatory process and it has a potential role in RA pathogenesis and prognosis. Further multicenter studies are needed to confirm these findings.

scholarly journals Vitamin D and Vitamin D Receptor in Scleroderma Subtypes

2020 ◽  
pp. 19-24
Author(s):  
Kocak Ayse
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Mrna Levels ◽  
Diffuse Type ◽  
Gene Expressions ◽  
Vdr Gene ◽  
Vitamin D Levels ◽  
Significant Difference ◽  
Tgf Β1

Vitamin D Receptor (VDR) is a member of the nuclear hormone receptor family. 1,25(OH)2D, a form of metabolically active vitamin D3 form, is the ligand of VDR. When VDR and 1,25(OH)2D are connected, many genes start to molecular interaction reactions that will modulate the transcription. VDR has been shown to be a negative regulator of the transforming growth factor beta-1 / Smad (TGF-β1 / Smad) signalling pathway. TGF-β1 / Smad signalling is important in the pathogenesis of scleroderma (SSc). Vitamin D has pleiotropic effects including immunomodulatory and antifibrotic properties in scleroderma pathogenesis. The aim of this study was to investigate the expression of VDR and the levels of vitamin D in scleroderma subtypes and study the possible correlation between the two parameters. 28 SSc patients and 30 healthy controls were included in the study and they were classified according to the 2013 ACR / EULAR criteria and Rodnan Scores were calculated. 14 were of the limited type and 14 were of the diffuse type of scleroderma. Vitamin D levels were determined in serum. Vitamin D level was measured by chemiluminescence immunometric assay. VDR gene expression was determined by quantitative PCR in isolated RNAs from the blood. Changes in mRNA levels were analysed and beta-actin was used as the housekeeping gene. Also, TGF-β1 gene expressions were determined. VDR gene expressions in diffuse type scleroderma patients were significantly decreased compared to the control. TGF-β1 gene expressions were increased in diffuse type scleroderma. It was found that VDR gene expression in limited type scleroderma patients did not show any significant difference when compared to control. Vitamin D levels and VDR gene expressions showed no correlation in scleroderma subtypes. VDR gene expression decreased in patients with diffuse type scleroderma and showed negative correlation with the Rodnan score and TGF-β1 gene expressions. There was no significant difference between vitamin D and VDR levels.

scholarly journals Mouse and Human BAC Transgenes Recapitulate Tissue-Specific Expression of the Vitamin D Receptor in Mice and Rescue the VDR-Null Phenotype

Endocrinology ◽  
2014 ◽  
Vol 155 (6) ◽  
pp. 2064-2076 ◽  
Author(s):  
Seong Min Lee ◽  
Kathleen A. Bishop ◽  
Joseph J. Goellner ◽  
Charles A. O'Brien ◽  
J. Wesley Pike
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Null Mouse ◽  
Vdr Gene ◽  
Specific Expression ◽  
Tissue Specific ◽  
Artificial Chromosomes ◽  
Tissue Specific Expression

The biological actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) are mediated by the vitamin D receptor (VDR), which is expressed in numerous target tissues in a cell type-selective manner. Recent studies using genomic analyses and recombineered bacterial artificial chromosomes (BACs) have defined the specific features of mouse and human VDR gene loci in vitro. In the current study, we introduced recombineered mouse and human VDR BACs as transgenes into mice and explored their expression capabilities in vivo. Individual transgenic mouse strains selectively expressed BAC-derived mouse or human VDR proteins in appropriate vitamin D target tissues, thereby recapitulating the tissue-specific expression of endogenous mouse VDR. The mouse VDR transgene was also regulated by 1,25(OH)2D3 and dibutyryl-cAMP. When crossed into a VDR-null mouse background, both transgenes restored wild-type basal as well as 1,25(OH)2D3-inducible gene expression patterns in the appropriate tissues. This maneuver resulted in the complete rescue of the aberrant phenotype noted in the VDR-null mouse, including systemic features associated with altered calcium and phosphorus homeostasis and disrupted production of parathyroid hormone and fibroblast growth factor 23, and abnormalities associated with the skeleton, kidney, parathyroid gland, and the skin. This study suggests that both mouse and human VDR transgenes are capable of recapitulating basal and regulated expression of the VDR in the appropriate mouse tissues and restore 1,25(OH)2D3 function. These results provide a baseline for further dissection of mechanisms integral to mouse and human VDR gene expression and offer the potential to explore the consequence of selective mutations in VDR proteins in vivo.

Vitamin D Receptor Gene Polymorphisms and the Risk of Metabolic Syndrome (MetS): A Meta-Analysis

2020 ◽  
Vol 20 ◽  
Author(s):  
Hamidreza Totonchi ◽  
Ramazan Rezaei ◽  
Shokoofe Noori ◽  
Negar Azarpira ◽  
Pooneh Mokarram ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Protective Factor ◽  
Meta Analysis ◽  
Receptor Gene ◽  
Fixed Effect Model ◽  
Fixed Effect ◽  
Vdr Gene ◽  
Effect Model

Introduction: Several studies have assessed the association between the vitamin D receptor (VDR) polymorphism and risk of metabolic syndrome (MetS). However, the results were inconsistent and inconclusive. Therefore, we conducted a meta-analysis to clarify the exact association between the vitamin D receptor (VDR) polymorphisms and the risk of MetS. Methods: All accessible studies reporting the association between the FokI (rs2228570) or / and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232 polymorphisms of the Vitamin D Receptor and susceptibility to MetS published prior to February 2019 were systematically searched in Web of Science, Scopus, and PubMed. After that, Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated to evaluate the strength of the association in five genetic models. Results: A total of 9 articles based on four gene variations, and comprising 3348 participants with 1779 metabolic syndrome patients were included. The overall results suggested a significant association between BsmI (rs1544410) polymorphism and MetS susceptibility in recessive model (OR, 0.72, 95% CI, 0.55-0.95, fixed effect model), allelic model (OR, 0.83, 95% CI, 0.72-0.95, fixed effect model), and bb vs BB (OR, 0.65, 95% CI, 0.46-0.93, fixed effect). However, no significant association was identified between TaqI (rs731236) polymorphism, ApaI (rs7975232) polymorphism, and FokI (rs2228570) polymorphism and MetS. Conclusion: This meta-analysis suggested an association between the BsmI (rs1544410) polymorphism and MetS. Indeed, BsmI (rs1544410) acts as a protective factor in the MetS. As a result, the VDR gene could be regarded as a promising pharmacological and physiological target in prevention or treatment of the MetS.

scholarly journals Study of vitamin D receptor gene polymorphisms in a cohort of myocardial infarction patients with coronary artery disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Damir Raljević ◽  
Viktor Peršić ◽  
Elitza Markova-Car ◽  
Leon Cindrić ◽  
Rajko Miškulin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Vitamin D ◽  
Coronary Artery ◽  
Vitamin D Receptor ◽  
Gene Polymorphisms ◽  
Vdr Gene ◽  
Vdr Polymorphism ◽  
Vdr Gene Polymorphisms ◽  
Vdr Polymorphisms

Abstract Background Vitamin D deficiency is associated with cardiovascular diseases, including coronary artery diseases (CAD). As vitamin D manifests its biological function through its vitamin D receptor (VDR), VDR gene polymorphisms potentially affect VDR functionality and vitamin D activity. Therefore, the objective of this study was to analyze three well-studied VDR gene polymorphisms—Fok1 (rs2228570), BsmI (rs1544410) and Taq1 (rs731236)—in a cohort of CAD patients after acute myocardial infarction. Methods In the presented cross-sectional study, 155 participants with CAD after acute myocardial infarction and 104 participants in a control group without CAD were enrolled. The participants in both groups were Caucasians of European origin. The genotyping of VDR polymorphisms rs2228570, rs1544410 and rs731236 was assessed by RT-PCR. Results The results show an association between the T/T genotype of the BsmI (rs1544410) and the G/G genotype of the Taq1 (rs731236) VDR polymorphism and CAD patients after acute myocardial infarction. There was no association between the Fok1 (rs2228570) VDR polymorphism and CAD patients after acute myocardial infarction. Conclusion The presented results suggest a potential association of the BsmI (rs1544410) and Taq1 (rs731236) VDR polymorphisms with CAD patients after myocardial infarction.

Past environmental sun exposure and risk of multiple sclerosis: a role for the Cdx-2 Vitamin D receptor variant in this interaction

2009 ◽  
Vol 15 (5) ◽  
pp. 563-570 ◽  
Author(s):  
JL Dickinson ◽  
DI Perera ◽  
AF van der Mei ◽  
A-L Ponsonby ◽  
AM Polanowski ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Significant Interaction ◽  
Important Determinant ◽  
Sun Exposure ◽  
Population Based ◽  
Vdr Gene ◽  
Increased Risk ◽  
Group 2

Multiple studies have provided evidence for an association between reduced sun exposure and increased risk of multiple sclerosis (MS), an association likely to be mediated, at least in part, by the vitamin D hormonal pathway. Herein, we examine whether the vitamin D receptor ( VDR), an integral component of this pathway, influences MS risk in a population-based sample where winter sun exposure in early childhood has been found to be an important determinant of MS risk. Three polymorphisms within the VDR gene were genotyped in 136 MS cases and 235 controls, and associations with MS and past sun exposure were examined by logistic regression. No significant univariate associations between the polymorphisms, rs11574010 ( Cdx-2A > G), rs10735810 ( Fok1T >  C), or rs731236 ( Taq1C > T) and MS risk were observed. However, a significant interaction was observed between winter sun exposure during childhood, genotype at rs11574010, and MS risk ( P = 0.012), with the ‘G’ allele conferring an increased risk of MS in the low sun exposure group (≤2 h/day). No significant interactions were observed for either rs10735810 or rs731236, after stratification by sun exposure. These data provide support for the involvement of the VDR gene in determining MS risk, an interaction likely to be dependent on past sun exposure.

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