scholarly journals Presence of a Truncated Form of the Vitamin D Receptor (VDR) in a Strain of VDR-Knockout Mice

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5581-5586 ◽  
Author(s):  
Craig M. Bula ◽  
Johanna Huhtakangas ◽  
Christopher Olivera ◽  
June E. Bishop ◽  
Anthony W. Norman ◽  
...  
Keyword(s):  
Vitamin D ◽  
Mouse Model ◽  
Vitamin D Receptor ◽  
Dissociation Constants ◽  
Specific Binding ◽  
Pcr Analysis ◽  
Wild Type ◽  
Truncated Form ◽  
Vdr Gene ◽  
Exon 2

As part of our studies on the membrane-initiated actions of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] and its localization in caveolae membrane fractions, we used a vitamin D receptor (VDR)-knockout (KO) mouse model to study the binding of [3H]-1α,25(OH)2D3 in the presumed absence of the VDR. In this mouse model, known as the Tokyo strain, the second exon of the VDR gene, which encodes the first of the two zinc fingers responsible for DNA binding, was removed, and the resulting animals have been considered to be VDR-null mice. To our surprise, several tissues in these KO mice showed significant (5–50% of that seen in wild-type animals) specific binding of [3H]-1α,25(OH)2D3 in nuclear and caveolae membrane fractions. The dissociation constants of this binding in samples from VDR-KO and wild-type mice were indistinguishable. RT-PCR analysis of intestinal mRNA from the VDR-KO animals revealed an mRNA that lacks exon 2 but contains exons 3–9 plus two 5′-untranslated exons. Western analysis of intestinal extracts from VDR-KO mice showed a protein of a size consistent with the use of Met52 as the translational start site. Transfection of a plasmid construct containing the sequence encoding the human analog of this truncated form of the receptor, VDR(52-C), into Cos-1 cells showed that this truncated form of the receptor retains full [3H]-1α,25(OH)2D3 binding ability. This same construct was inactive in transactivation assays using the osteocalcin promoter in CV1 cells. Thus, we have determined that this widely used strain of the VDR-KO mouse can express a form of the VDR that can bind ligand but not activate gene transcription.

scholarly journals Association between Vitamin D Level, Vitamin D Receptor Gene Polymorphisms, and Cathelicidin Level to Acute Lower Respiratory Infections, and the Picture of Exon 2-Vitamin D Receptor Gene Polymorphisms in Children under 5 years old

2020 ◽  
Vol 8 (B) ◽  
pp. 536-541
Author(s):  
Ida Bagus Subanada ◽  
I. Made Bakta ◽  
I. Wayan Bikin Suryawan ◽  
Putu Astawa ◽  
Bagus Komang Satriyasa
Keyword(s):  
Risk Factors ◽  
Vitamin D ◽  
Gene Polymorphism ◽  
Vitamin D Deficiency ◽  
Vitamin D Receptor ◽  
Gene Polymorphisms ◽  
Vdr Gene ◽  
Exon 2 ◽  
Vdr Gene Polymorphism ◽  
Low Levels

BACKGROUND: Acute lower respiratory infections (ALRIs) are infectious diseases with high morbidity and mortality in children under five. There are several factors associated with ALRIs (bronchiolitis or pneumonia) that have been established. In recent years, Vitamin D level, Vitamin D receptor (VDR) gene polymorphism, and cathelicidin level are also associated with ALRIs. Until now, there was no VDR gene other than Fok1 identified at the exon 2-VDR gene. OBJECTIVE: The objective of this study was to establish whether Vitamin D deficiency, ff genotype-Fok1 VDR gene polymorphism, and low levels of cathelicidin are risk factors of ALRIs and to determine the pictures of exon 2-VDR genes polymorphisms in children under five. METHODS: A matched case–control study was conducted in children under the age of five. There were 35 subjects who suffered from bronchiolitis or pneumonia and 35 healthy subjects as a control group. These groups were matched based on age and gender, and the children originated from the same neighborhood. Level of 25(OH) D, exon 2-VDR genes sequencing, and level of cathelicidin were investigated. Data were analyzed by the Chi-square test or Fisher exact test and logistic regression with a significant level of p < 0.05. RESULTS: This study found that Vitamin D deficiency and low levels of cathelicidin were risk factors of ALRIs (odds ratio [OR] = 5.82 [95% confidence interval [CI] = 1.71–19.89], p = 0.005 and OR = 4.07 [95% CI = 1.10–15.12], p = 0.036, respectively), while ff genotype-Fok1 VDR gene polymorphism was not (OR = 1.12 [95% CI = 0.26–4.86], p = 1.000). Fok1 VDR gene polymorphism was the picture of exon 2-VDR gene polymorphisms. CONCLUSION: It is concluded that Vitamin D deficiency and low levels of cathelicidin are risk factors, but ff genotype-Fok1 VDR gene polymorphism is not a risk factor of ALRIs. Fok1 VDR gene polymorphism is the picture of exon 2-VDR genes polymorphisms.

scholarly journals A reappraised meta-analysis of the genetic association between vitamin D receptor BsmI (rs1544410) polymorphism and pulmonary tuberculosis risk

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Mohammed Y. Areeshi ◽  
Raju K. Mandal ◽  
Sajad A. Dar ◽  
Abdulrahman M. Alshahrani ◽  
Aqeel Ahmad ◽  
...  
Keyword(s):  
Vitamin D ◽  
Pulmonary Tuberculosis ◽  
Vitamin D Receptor ◽  
Meta Analysis ◽  
Genetic Models ◽  
Wild Type ◽  
Vdr Gene ◽  
Bsmi Polymorphism ◽  
Increased Risk ◽  
Tuberculosis Risk

BsmI (rs1544410) polymorphism located in intron 8 at the 3′-end of the vitamin D receptor (VDR) gene is known to be involved in the regulation of mRNA stability. Many studies evaluated the possible correlation between VDR BsmI polymorphism and the risk of pulmonary tuberculosis (PTB), and reported conflicting results. In the present study, an updated meta-analysis was performed to evaluate the above-said association. PubMed, Embase, and Google Scholar web-databases were searched for the relevant studies and a meta-analysis was performed by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for all the genetic models. A total of 19 studies comprising 3644 controls and 2635 cases were included in the present study. Overall no association of PTB in allelic contrast (b compared with B: P=0.285; OR =0.909, 95% CI =0.762–1.083), homozygous (bb compared with BB: P=0.881; OR =0.975, 95% CI =0.700–1.359), heterozygous (bB compared with BB: P=0.834; OR =1.017, 95% CI =0.872–1.185), dominant (bb compared with BB + Bb: P=0.451; OR =0.954, 95% CI =0.843–1.079) and recessive (bb + Bb compared with BB: P=0.983; OR =1.002, 95% CI =0.868–1.156) genetic models in comparison with wild-type allele and genotype BB were observed. However, variant allele (b compared with B: P=0.001; OR =2.289, 95% CI =1.661–3.154) showed increased risk of PTB in Asians. In conclusion, VDR BsmI polymorphism is not a risk factor for PTB in overall population. However, this polymorphism may be interrelated to an increased risk of PTB amongst Asians.

scholarly journals Vitamin D Receptor Gene Polymorphisms in Susceptibility to Tuberculosis in the Kazakh Population in Almaty and Almaty Area

2014 ◽  
Vol 2 ◽  
Author(s):  
Maxat Zhabagin ◽  
Zhannur Abilova ◽  
Ayken Askapuli ◽  
Saule Rakhimova ◽  
Ulykbek Kairov ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Gene Polymorphisms ◽  
Disease Risk ◽  
Mononuclear Phagocytes ◽  
Control Analysis ◽  
Vdr Gene ◽  
Exon 2 ◽  
Kazakh Population ◽  
Vdr Gene Polymorphisms

Introduction: Vitamin D receptor (VDR) plays an important role in activating the immune response against various infectious agents. It is known that the active metabolite of ligand receptor Vitamin D (1,25 – dihydroxyvitamin D) is encoded by VDR and helps mononuclear phagocytes to suppress the intracellular growth of M. tuberculosis. The VDR gene harbors approximately 200 polymorphisms, some of which are linked to differences in receptor Vitamin D uptake and therefore can be considered as candidate disease risk variants. The relation between VDR gene polymorphisms and susceptibility to TB has been studied in different populations. There is not a great deal of information regarding the association of these SNPs with TB risk in the Kazakh population. The four most commonly investigated VDR polymorphisms in association with different diseases, including susceptibility to tuberculosis, are located in exon 2 (rs2228570 or FokI), intron 8 (rs1544410 or BsmI and rs7975232 or ApaI), and exon 9 (rs731236 or TaqI). The aim of our study was to determine whether these four VDR gene single nucleotide polymorphisms were associated with TB and whether they were a risk for the development of TB in the Kazakh Population in Almaty city and Almaty area.Methods: This study was a hospital-based case-control analysis of 283 individuals (99 TB patients and 184 healthy controls). Genotyping was performed by Taqman SNP allelic discrimination using commercial TaqMan SNP Genotyping assays.  Statistical analysis was conducted using SPSS Version 19.0 software.Results: Genotype frequencies for the Kazakh population are close to world (HapMap) data on Asian populations. FokI and ApaI polymorphisms genotypes tend to be associated with TB risk under the co-dominant model [OR=1.18; 95%CI: (0.68, 2.07), p=0.15] for FokI and [OR=1.33; 95%CI: (0.61, 2.91), p=0.6] for ApaI. No significant association between the disease and TaqI, BsmI genotypes was observed.Conclusions: In summary, we explored potential associations between SNPs in the VDR (FokI, ApaI) gene and susceptibility to tuberculosis in the Kazakh Population, which requires further detailed analysis with a larger sample size and greater geographic diversity including other regions of Kazakhstan.

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.

scholarly journals The Vitamin D Receptor (VDR) Gene Polymorphisms in Turkish Brain Cancer Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Bahar Toptaş ◽  
Ali Metin Kafadar ◽  
Canan Cacina ◽  
Saime Turan ◽  
Leman Melis Yurdum ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cancer Patients ◽  
Vitamin D Receptor ◽  
Brain Cancer ◽  
Gene Polymorphisms ◽  
Vdr Gene ◽  
Increased Risk ◽  
Vdr Gene Polymorphisms ◽  
Significant Difference ◽  
Healthy Control

Objective. It has been stated that brain cancers are an increasingly serious issue in many parts of the world. The aim of our study was to determine a possible relationship between Vitamin D receptor (VDR) gene polymorphisms and the risk of glioma and meningioma.Methods. We investigated the VDR Taq-I and VDR Fok-I gene polymorphisms in 100 brain cancer patients (including 44 meningioma cases and 56 glioma cases) and 122 age-matched healthy control subjects. This study was performed by polymerase chain reaction-based restriction fragment length polymorphism (RF LP).Results. VDR Fok-I ff genotype was significantly increased in meningioma patients (15.9%) compared with controls (2.5%), and carriers of Fok-I ff genotype had a 6.47-fold increased risk for meningioma cases. There was no significant difference between patients and controls for VDR Taq-I genotypes and alleles.Conclusions. We suggest that VDR Fok-I genotypes might affect the development of meningioma.

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