Vitamin D Receptor Gene In Patients Research Articles

A study of the association of vitamin D receptor (VDR) as a predictive biomarker for immune checkpoint inhibitor therapy with immune invasion in colon adenocarcinoma

Colon adenocarcinoma(COAD) is a primary and aggressive malignancy with the fifth highest mortality rate among cancers, and it is important to discover new strategies. The online database was used to analyze the correlation between Vitamin D receptor (VDR) and COAD, and further explore the immune infiltration and related gene networks.The expression and methylation levels of VDR was analyzed by using Timer database, GEPIA platform and UALCAN database. GeneMANIA database was used to analyze and obtain gene networks that are closely linked to VDR. UALCAN database was used to score the gene effects of VDR in colorectal cancer cell lines. The cBioPortal database was used for the detection of gene mutations. The survival curve analysis was carried out using the GEPIA database. The relationship between VDR expression and immune cell infiltration was analyzed by using the timer database and TISIDB database. TISIDB database was used to obtain VDR-related drug targets.The expression of VDR was significantly lower in COAD(p<0.05). The methylation level of VDR was significantly higher in COAD (p<0.05). The gene mutation rate of VDR in COAD was 2 %. OS and DFS were not associated with changes in the VDR gene in patients with COAD. VDR expression was correlated with CD4+T cell infiltration, macrophage infiltration, neutrophil infiltration, and dendritic cell infiltration. VDR has a clear correlation with ADORA2A, BTLA, CD160, CD244, CD274, CD96, CSF1R, CTLA4, HAVCR2, IL10, IDO1, LAG3, LGALS9, PDCD1, PDCD1LG2, PVRL2, TGFB1, TGFBR1, TIGIT and VTCN1.The expression of VDR is associated with immune infiltration in patients with COAD. VDR may be a new candidate biomarker for determining the level of immune infiltration and predicting immune checkpoint inhibitor therapy.

Correlation of polymorphous variants (ApaI, TagI, BsmI) of the VDR receptor gene with the vitamin D level and liver fibrosis in children with autoimmune hepatitis

The aim. To study the correlation of the frequency distribution of alleles, genotypes and their combinations for the allelic variants of ApaI, TagI, BsmI of the Vitamin D receptor gene (VDR) with the vitamin D levels and the stage of fibrosis in children with autoimmune hepatitis.Materials and methods. 51 children with autoimmune hepatitis were examined between 2016 and 2018. In all children, the diagnosis was confirmed in accordance with the International Guidelines for the study of liver diseases (European Association for the Study of Liver (EASL) Clinical Practice Guidelines: Autoimmune Hepatitis, 2015). In the examined children, the elastography of the liver parenchyma was performed by the shear wave method. Needle biopsy of the liver with histological examination of the specimens was performed in 42 children. The disease activity was determined using the histological activity index (HAI) by Knodell based on the results of a morphological study of the liver biopsy and biochemical parameters. The stage of the disease was evaluated by the histological index of fibrosis using the METAVIR scoring system and semi-quantitatively using the share wave elastography of liver parenchyma. A level of 25(OH)D was determined in the blood serum. The determination of the ApaI, TagI, BsmI polymorphic loci of vitamin D receptor (VDR) was carried out using the molecular-genetic method. The association of polymorphic variants of the VDR gene with the level of vitamin D and the stage of liver fibrosis in children with autoimmune hepatitis has been evaluated.Results. 72.0 % of the examined children had advanced severe liver fibrosis (F3-4 by the METAVIR score), among them 34.0 % of children had signs of liver cirrhosis. Children with advanced severe fibrosis (F3–4 by the METAVIR score) had the CC genotype of the polymorphic version of the TagI of the VDR gene significantly more often (χ2 = 3.953; P &lt; 0.05), and the genotype AA/CC/AA according to the investigated allelic variants of the VDR gene (χ2 = 3.953; P &lt; 0.05). In 72.5 % of the examined children, there was a deficiency of vitamin D. In children with severe fibrosis (F3–4 by the METAVIR score) vitamin D deficiency was significantly more frequent as compared to children with less severe fibrosis (F1–2 by the METAVIR score) (χ2 = 5,207; P = 0.023). The genotype GA of the BsmI polymorphic variant was associated with a decrease in serum vitamin D levels (P &lt; 0.05). At the AC/TC/GA combination of the ApaI, TagI and BsmI allelic variants of the VDR gene, vitamin D deficiency was registered significantly more frequently (P &lt; 0.05).Conclusions. The level of vitamin D in children with autoimmune hepatitis was dependent on the stage of fibrosis. Children with severe fibrosis had a genetically determined vitamin D deficiency significantly more often. Vitamin D deficiency was associated with the CC genotype presence of the TagI polymorphic variant of the VDR gene in patients as well as the GA genotype of the BsmI polymorphic variant and the AC/TC/GA genotype of the three allelic variants of the gene studied.

Vitamin D receptor mutations in patients with hereditary 1,25-dihydroxyvitamin D-resistant rickets

ContextHereditary vitamin D resistant rickets (HVDRR), also known as vitamin D-dependent rickets type II, is an autosomal recessive disorder characterized by the early onset of rickets with hypocalcemia, secondary hyperparathyroidism and hypophosphatemia and is caused by mutations in the vitamin D receptor (VDR) gene. The human gene encoding the VDR is located on chromosome 12 and comprises eight coding exons and seven introns. Objectives, patients, and methodsWe analyzed the VDR gene of 5 previously unreported patients, two from Singapore and one each from Macedonia (former Yugoslav Republic), Saudi Arabia and Turkey. Each patient had clinical and radiographic features of rickets, hypocalcemia, and the 4 cases that had the measurement showed elevated serum concentrations of 1,25-dihydroxyvitamin D (1,25(OH)2D). Mutations were re-created in the WT VDR cDNA and examined for 1,25(OH)2D3-mediated transactivation in COS-7 monkey kidney cells. ResultsDirect sequencing identified four novel mutations and two previously described mutations in the VDR gene. The novel mutations included a missense mutation in exon 3 causing the amino acid change C60W; a missense mutation in exon 4 causing the amino acid change D144N; a missense mutation in exon 7 causing the amino acid change N276Y; and a 2bp deletion in exon 3 5′-splice site (IVS3∆+4–5) leading to a premature stop. ConclusionsThese 4 unique mutations add to the previous 45 mutations identified in the VDR gene in patients with HVDRR.

Vitamin D and polymorphisms of VDR gene in patients with systemic lupus erythematosus

The susceptibility for the development of systemic lupus erythematosus (SLE) is related to environmental, hormonal, genetic, and immunological factors. Numerous genes have been linked to the emergence of SLE, including vitamin D receptor (VDR) gene that synthesizes the receptor of vitamin D. Several polymorphisms have been described since the discovery of this gene, and their effects on VDR activity are still poorly understood. Vitamin D's biological functions are mediated by VDR. Vitamin D exerts many actions on the immune system, and several studies have suggested its role in the pathogenesis of autoimmune diseases. SLE patients have low blood levels of vitamin D, which raises the possibility of association between the deficiency of this vitamin and the onset of the disease. BsmI and FokI polymorphic variants seem to be related to the onset of the disease in Asian patients. In this article, we review the aspects related to the metabolism and immunoregulatory effects of vitamin D, VDR, and main polymorphisms involving the VDR gene and the relationship between vitamin D levels and its receptor with SLE.

Gender-specific association of vitamin D receptor polymorphism combinations with type 1 diabetes mellitus

Recent data have indicated the significance of vitamin D receptor (VDR) polymorphisms in type 1 diabetes mellitus (T1DM). We have studied the association of five known restriction enzyme polymorphisms of the VDR gene in patients with T1DM. One hundred and seven children with T1DM (T1DM for 5 Years; age, 1-14 Years; boys/girls, 57/50; body mass index, 17.0+/-2.3 kg/m(2); haemoglobin A(Ic) (HbA(Ic)), 7.87+/-1.05) and 103 healthy subjects were enrolled. The VDR polymorphisms ApaI, BsmI, FokI, TaqI and Tru9I ("a", "b", "f", "t" and "u" alleles respectively) were investigated. The "t" and "T" alleles miss the Hardy-Weinberg equilibrium (P<0.01) in control and diabetic populations; we therefore excluded this polymorphism from further analysis. We did not find a difference in the allele prevalence in T1DM patients and controls of any of the five polymorphisms. However, when the "b", "a" and "u" alleles were simultaneously compared in girls, there was a significantly higher prevalence in patients with diabetes compared with controls ("b"+"a"+"u" present/absent: healthy, 0/53; diabetic, 13/37; P<0.005). In boys the prevalence of "b"+"a"+"u" genotype was similar in T1DM and controls. The impact of the "t" allele cannot be investigated in this study population. Not a single VDR polymorphism increases the susceptibility to T1DM. The common presence of the "b", "a" and "u" alleles greatly increases the probability of T1DM in girls.