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Correlations among Pulmonary DJ-1, VDR and Nrf-2 in patients with Chronic Obstructive Pulmonary Disease: A Case-control Study.
Xiang, Y, Fu, L, Xiang, HX, Zheng, L, Tan, ZX, Wang, LX, Cao, W, Xu, DX, Zhao, H
International journal of medical sciences. 2021;(11):2449-2456
Abstract
Parkinson protein 7 (PARK7)/DJ-1 (DJ-1) is a redox sensitive molecular and stabilizer of nuclear factor erythroid 2-related factor 2 (Nrf-2). Nrf-2 regulates the downstream antioxidant defense system and exerts a significant function in patients with chronic obstructive pulmonary disease (COPD). Vitamin D receptor (VDR) is the nuclear receptor that regulates the downstream target genes. This study aimed to analyze the associations among pulmonary function, DJ-1, VDR and Nrf-2 in COPD patients. Serum was collected from 180 COPD patients and control subjects. Thirty-five lung tissues were obtained. DJ-1 was measured using ELISA and western blotting. Nrf-2 and VDR were detected by immunohistochemistry. Serum and pulmonary DJ-1 levels were lower in COPD patients than those in control subjects. Pulmonary VDR-positive nuclei were reduced in COPD patients. Nrf-2-positive nuclei were reduced in lung tissues of COPD patients. On the contrary, Nrf-2-related downstream target proteins were elevated in COPD patients. Further correlation analysis indicated that forced expiratory volume in 1 second (FEV1) was positively associated with pulmonary DJ-1, VDR and Nrf-2 in patients with COPD. In addition, there were positive correlations among DJ-1, VDR and Nrf-2 in lung tissues of COPD patients. In conclusion, DJ-1, VDR and Nrf-2 were decreased in COPD patients compared with control subjects. The reduction of DJ-1 and VDR associating with Nrf-2 downregulation may be involved in the process of COPD.
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Study of vitamin D receptor gene polymorphisms in a cohort of myocardial infarction patients with coronary artery disease.
Raljević, D, Peršić, V, Markova-Car, E, Cindrić, L, Miškulin, R, Žuvić, M, Kraljević Pavelić, S
BMC cardiovascular disorders. 2021;(1):188
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.
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MiR-125b promotes migration and invasion by targeting the vitamin D receptor in renal cell carcinoma.
He, X, Liao, S, Lu, D, Zhang, F, Sun, Y, Wu, Y
International journal of medical sciences. 2021;(1):150-156
Abstract
Purpose: To investigate the expression of miR-125b and vitamin D receptor (VDR) in renal cell carcinoma (RCC) and assess the biological function of miR-125b in RCC. Methods: We used quantitative real-time polymerase chain reaction (RT-PCR) to detect the expression of nucleic acids and western blotting to analyze the protein abundance in RCC cell lines. MiR-125b mimic and inhibitor were employed to investigate the function and behavior of miR-125b in RCC cell lines. The relationship between miR-125 and VDR was verified using luciferase assays. Results: Overexpression of miR-125b promoted migration and invasion and prevent cell apoptosis in ACHN cells. In contrast, miR-125b deficiency suppressed migration and invasion and induced cell apoptosis in 786-O cells. Luciferase assays indicated the interaction between miR-125b and VDR. In collected samples, miR-125b was significantly higher in RCC tissues and negatively correlated to VDR (r=-0.444, p=0.04). Conclusion: MiR-125b displays an oncogene profile in RCC, patients with high expression of miR-125b should be a more frequent follow-up. MiR-125B may be a potential therapeutic target for RCC.
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Expression of vitamin D receptor, CYP27B1 and CYP24A1 hydroxylases and 1,25-dihydroxyvitamin D3 levels in stone formers.
Melo, TL, Esper, PLG, Zambrano, LI, Ormanji, MS, Rodrigues, FG, Heilberg, IP
Urolithiasis. 2020;(1):19-26
Abstract
The expression of vitamin D receptor (VDR) and 1,25-dihydroxyvitamin D3 [1,25(OH)D] levels exceed the values of controls in some but not all hypercalciuric stone formers (HSF). We aimed to evaluate serum 1,25(OH)D levels, the expression of VDR, CYP27B1, and CYP24A1 hydroxylases in HSF in comparison with normocalciuric stone formers (NSF) and healthy subjects (HS). Blood samples, 24-h urine collections and a 3-day dietary record were obtained from 30 participants from each of the groups. The expression of VDR, CYP27B1, and CYP24A1 was measured by flow cytometry. HSF presented significantly higher urinary volume, sodium, magnesium, oxalate, uric acid, and phosphorus than NSF and HS. Calcium intake was lower in HSF versus NSF and HS (442 ± 41 vs 594 ± 42 and 559 ± 41 mg/day, respectively, p = 0.027). Ionized calcium was significantly lower in HSF than NSF (1.29 ± 0.0 vs 1.31 ± 0.0 mmol/L, p < 0.01). Serum 1,25(OH)D was significantly higher in HSF and NSF than HS (22.5 ± 1.2; 22.2 ± 1.2 vs 17.4 ± 1.2 pg/ml, p = 0.007) but serum 25(OH)D, PTH, klotho and plasma FGF-23 did not differ between groups. VDR expression was higher in HSF and NSF than HS (80.8 ± 3.2; 78.7 ± 3.3 vs 68.6 ± 3.2%, p = 0.023). Although CYP27B1 and CYP24A1 expressions were similar among all groups, the ratio of 1,25(OH)D/CYP24A1 was higher in HSF and NSF than in HS (1.43 ± 0.25 and 0.56 ± 0.10 vs 0.34 ± 0.06, p = 0.00). Stone formers, regardless of urinary calcium excretion, had higher VDR expression and 1,25(OH)D levels than HS, even in ranges considered normal. Higher 1,25(OH)D/CYP24A1 ratio suggested a lower degradation of 1,25(OH)D by CYP24A1 in HSF and NSF.
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Impact of vitamin D receptor and binding protein gene polymorphisms in clinical and laboratory data of HCV patients: Cross sectional study.
Scalioni, LP, Santos, BRD, Spritzer, PM, Villela-Nogueira, CA, Laura Lewis-Ximenez, L, Pollo-Flores, P, Bordalo Cathalá Esberard, E, Brandão-Mello, CE, Lampe, E, Villar, LM
Medicine. 2018;(8):e9881
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Abstract
Potential relationship of vitamin D, vitamin D receptor (VDR), and vitamin D binding protein (DBP) have been suggested in the pathophysiology of hepatitis C virus (HCV) infection. The aim of this observational study is to determine vitamin D levels, and VDR and DBP genetic polymorphism according demographic and laboratory data in chronic HCV patients (CHC).A total of 148 CHC patients gave serum samples for testing 25-hydroxyvitamin D (25 (OH)D) level by immunochemiluminometric assay (<20 ng/mL defined as deficient) and donated blood samples to allelic discrimination analysis using TaqMan assays. Analyzed single nucleotide polymorphisms (SNPs) were: VDR-rs7975232 (ApaI) C>A, rs731236 A>G (TaqI), rs1544410 C>T (BsmI), rs10735810 T>C (FokI) and carrier globulin/binding protein (GC)-rs4588 and rs7041 and the haplotype bAt [CCA]. Hepatic fibrosis was assessed using Fib-4 and Forns index.Eighty-two (54.40%) patients demonstrated deficiency of vitamin D and this was associated to AST (P = .019 [CI: 1.003-1.034]), total cholesterol (P = .038 [CI: 1.004-1.164]), fibrosis grade (P < .001 [CI: 0.000-0.844]), and FokI (P = .028) allele T presence. Association was found between VDR polymorphism and fibrosis (BsmI andTaqI), triglycerides (TaqI), and HDL (FokI). DBP polymorphism was associated to HCV genotype (GC rs7041), previous HCV treatment, and GGT (GC rs4588).In conclusion, low frequency of vitamin D deficiency was found, but VDR polymorphisms were frequently associated to fibrosis grade suggesting that they could be used as disease evaluation markers to understand the mechanisms underlying the virus-host interaction.
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Etiologic risk factors and vitamin D receptor gene polymorphisms in under one-year-old infants with urolithiasis.
Ergon, EY, Akil, İO, Taneli, F, Oran, A, Ozyurt, BC
Urolithiasis. 2018;(4):349-356
Abstract
The incidence of urinary tract stones in infancy has been increasing in Turkey. Risk factors and vitamin D receptor (VDR) gene polymorphisms were investigated in infants aged < 1 year who had stones. Forty infants with urinary tract stones and 80 infants without stones, aged < 1 year were enrolled in this study. Detailed surveys were taken of all infants, metabolic parameters and ApaI and FokI VDR gene polymorphisms were investigated. Infants with stones tended to be more commonly fed formula and multivitamins (vitamins A, C, D) (p < 0.05). Positive family history came into prominence in the stony group (p < 0.05). There were no significant differences in ApaI and FokI VDR gene polymorphisms between the groups with stones and the control groups. However, CA genotype of ApaI polymorphism was associated with family history and C allele of ApaI was related with family history and hypercalciuria (p < 0.05). Hypercalciuria emerged as an underlying metabolic abnormality in the etiology of stones, and was observed at a rate of 38%. Infants who are given formula and multivitamins for vitamin D supplementation are at increased risk for the formation of urinary tract stones. VDR gene polymorphisms cause the formation of urinary tract stones and affect calcium (Ca) metabolism.
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Serum vitamin D level and vitamin D receptor genotypes may be associated with tuberculosis clinical characteristics: A case-control study.
Zhang, Y, Zhu, H, Yang, X, Guo, S, Liang, Q, Lu, Y, Chen, X
Medicine. 2018;(30):e11732
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Abstract
Vitamin D is associated with the susceptibility of tuberculosis and might have an adjunctive effect on anti-tuberculosis treatment. This study aims to investigate the association of vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms with susceptibility and severity to multidrug-resistant tuberculosis (MDR-TB) in comparison with drug-sensitive tuberculosis (DS-TB) and health controls in China.A total of 180 patients with pulmonary TB (128 DS-TB, 52 MDR-TB) and 59 healthy controls were enrolled into 3 groups. Vitamin D levels and VDR genotypes at FokI, BsmI, ApaI, and TaqI sites of all the participants and clinical characteristics of patients with TB were measured and collected.Statistical analysis revealed that vitamin D levels were lower in both TB groups. Patients with TB with bilateral lesions and patients with MDR-TB with extrapulmonary TB had lower vitamin D levels. The frequencies of ff genotype and f allele were higher in both TB groups. Patients with Ff genotype and ff genotype had lower proportion of extrapulmonary TB. Patients with ff genotype had higher proportion of retreatment. Male patients with ff genotype had higher proportion of cavity formation. Patients with DS-TB with AA genotype had higher proportion of cavity formation.Our findings demonstrate that vitamin D deficiency and ff genotype may be the risk factors of TB in Chinese population. In addition, patients with TB with lower level of vitamin D may have a greater risk of bilateral lesions and extrapulmonary TB. VDR genotypes may be associated with TB clinical characteristics.
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VITAMIN D RECEPTOR GENE MUTATIONS AND VITAMIN D SERUM LEVELS IN ASTHMATIC CHILDREN.
Santos, HLBS, Silva, SSE, Paula, E, Pereira-Ferrari, L, Mikami, L, Riedi, CA, Chong-Neto, HJ, Rosário, NA
Revista paulista de pediatria : orgao oficial da Sociedade de Pediatria de Sao Paulo. 2018;(3):269-274
Abstract
OBJECTIVE To verify the relationship between polymorphisms of the vitamin D receptor gene (VDR), clinical findings, and serum vitamin D (VD) levels in asthmatics. METHODS A cross sectional study of 77 children aged 7 to 14 years old, who were attended at a specialized clinic. The children were divided into 3 groups: asthmatics who had been using inhaled corticosteroids (ICS) for more than one year; asthmatics who had not been using ICS; non-asthmatics, and children without allergies (according to the International Study of Asthma and Allergies in Childhood -- ISAAC). Spirometry, skin prick tests, the presence of a VDR promoter CDX2 polymorphism from an allele-specific polimerase chain reaction (PCR), exons 2 and 3 polymorphisms genotyping by PCR-SSCA (single-strand conformational analysis), total immunoglobulin E (IgE) and specific IgE to mites and grass were evaluated in these three groups. Levels of 25-hydroxyvitamin D were determined in asthmatics only. RESULTS The mean age of the children was 10.8±2.0 years old, 57% were male, 38 were asthmatic and using ICS, 22 were asthmatic and not using ICS, and 17 were non-asthmatic. Allergic rhinitis was present in 90% of asthmatics. Homozygous CDX2 was detected in 23% of the patients and absent in the control group (p=0.03). Lower forced expiratory volume in 1 second (FEV1%) values were observed in CDX2 homozygous asthmatics (p=0.001). Variations in the exon 2 and 3 sequences were not related to asthma or the other tests. VD deficiency or insufficiency was detected in 98% of asthmatics. There was no association between VD levels and genetic polymorphisms from exons 2 and 3. CONCLUSIONS There was a positive association between homozygous CDX2 polymorphism, asthma and lower FEV1% values. CDX2 is capable of modifying cell interaction between VDR and VD, and it could be associated with the prevalence of asthma, and the difficulty in controlling the disease.
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Predialysis Vitamin D Receptor Activator Treatment and Cardiovascular Events after Dialysis Initiation: A Multicenter Observational Study.
Inaguma, D, Tanaka, A, Shinjo, H, Kato, A, Murata, M, ,
Nephron. 2016;(1):35-43
Abstract
BACKGROUND Vitamin D receptor activator (VDRA) administration has been linked with a reduced incidence of cardiovascular disease (CVD). However, it is unclear whether VDRA administration during the predialysis stage is associated with CVD incidence after dialysis initiation in patients with chronic kidney disease. Therefore, we examined the association between VDRA use and CVD events. METHODS This multicenter observational study included 1,516 patients; they were divided into 2 groups: those who did and did not receive oral VDRA for at least 3 months before dialysis initiation. The CVD incidence was compared between these groups. Factors that impacted CVD incidence were extracted through a multivariate analysis. Subgroups were created based on prior CVD history and serum CRP levels. RESULTS The incidence of CVD was significantly lower in the VDRA group (log-rank test, p = 0.014). Stepwise multivariate analyses identified age, gender, diabetes, CVD history, calcium-channel blockers, beta-blockers, loop diuretics, anti-platelet agents, phosphate binders, VDRA, erythropoiesis stimulating agents, and cardiothoracic ratio as factors affecting CVD incidence. In the group with no CVD history, VDRA use was associated with a low incidence of CVD (HR 0.35). In the group with serum CRP levels <1.0 mg/dl, VDRA use was associated with a low incidence of CVD (HR 0.47). CONCLUSION Administration of VDRA during predialysis was associated with a low incidence of CVD onset after dialysis initiation.
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Effect of VDRA on survival in incident hemodialysis patients: results of the FARO-2 observational study.
Messa, P, Cozzolino, M, Brancaccio, D, Cannella, G, Malberti, F, Costanzo, AM, di Luzio Paparatti, U, Festa, V, Gualberti, G, Mazzaferro, S, et al
BMC nephrology. 2015;:11
Abstract
BACKGROUND Mortality rate among patients with stage five chronic kidney disease (CKD) maintained on hemodialysis (HD) is high. Although evidence suggests that use of Vitamin D Receptor Activators (VDRA) in CKD patients increases survival, few studies have examined the effect of VDRA in incident HD patients. The FARO-2 study evaluated the clinical outcome of VDRA therapy on mortality in incident HD patients. METHODS FARO-2 was a longitudinal epidemiological study performed on 568 incident HD patients followed prospectively from 26 dialysis centers over a 3-year period. Data were collected every 6 months using a questionnaire, obtaining clinical, biochemical and therapeutic parameters. Kaplan-Meier curves and Cox proportional hazard regression models were used to determine cumulative probability of time-to-death and adjusted hazard ratios. RESULTS 568 patients (68% male) with an average age of 65.5 years were followed up. Mean dialysis duration at study entry was 3 months. VDRA use increased from 46% at 6 months to 54.7% at 36 months of follow-up (p = 0.08). No difference was observed in the presence of comorbid diseases at baseline in patients with and without VDRA therapy. Cumulative probability of survival at 24 months was 74.5% (95% CI: 70.2-78.3). Patients receiving VDRA therapy showed a significant increase in survival at 24 months (80.7%; 95% CI: 75.7-84.8) compared to those without (63.3%; 95% CI: 54.8-70.7, p <0.01). The presence of vascular disease, decreased hemoglobin, increased P and lack of VDRA treatment were significantly associated with an increased risk of mortality. Lack of VDRA treatment still remained significant as a predictor of mortality after adjusting for levels of PTH, P and Ca (HR = 2.16, 95% CI: 1.09-4.30, p = 0.03). CONCLUSIONS Findings from FARO-2 indicate that in incident HD patients VDRA therapy was associated with increased survival.