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1.
Vitamin D: A Micronutrient Regulating Genes.
Carlberg, C
Current pharmaceutical design. 2019;(15):1740-1746
Abstract
BACKGROUND At sufficient sun exposure, humans can synthesize vitamin D3 endogenously in their skin, but today's lifestyle makes the secosteroid a true vitamin that needs to be taken up by diet or supplementation with pills. The vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 acts as a nuclear hormone activating the transcription factor vitamin D receptor (VDR). METHODS This review discusses the biological effects of micronutrient vitamin D ranging from calcium homeostasis and bone formation to the modulation of innate and adaptive immunity. RESULTS Since normal human diet is sufficient in vitamin D, the need for efficient vitamin D3 synthesis in the skin acts as an evolutionary driver for its lightening during the migration out of Africa towards North. Via activating the VDR, vitamin D has direct effects on the epigenome and the expression of more than 1000 genes in most human tissues and cell types. CONCLUSIONS The pleiotropic action of vitamin D in health and disease prevention is explained through complex gene regulatory events of the transcription factor VDR.
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2.
Molecular basis of vitamin D action in neurodegeneration: the story of a team perspective.
Gezen-Ak, D, Dursun, E
Hormones (Athens, Greece). 2019;(1):17-21
Abstract
Vitamin D, a secosteroid hormone, has, over the years, mainly been known for its classic role in the maintenance of calcium homeostasis of the human body. However, there is increasing understanding that vitamin D contributes to the regulation of Ca2+ homeostasis, especially via voltage-gated calcium channels, in another major organ that uses calcium, the brain. Almost 30 years ago, the role of dysregulation in the aging brain and in Alzheimer's disease (AD) gave rise to the Ca2+ hypothesis of brain aging and dementia. We thus made calcium homeostasis the starting point of our studies, proposing the notion that the consequences of long-term deficiency and/or inefficient utilization of vitamin D may cause the disruption of calcium homeostasis in neurons, this creating a vulnerability of neurons to aging and neurodegeneration. In this mini-review, we aim to describe the potential of vitamin D (cholecalciferol) as a neurosteroid based on our findings and conclusions.
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3.
Association of select vitamin D receptor gene polymorphisms with the risk of tobacco-related cancers - a meta-analysis.
Laczmanski, L, Laczmanska, I, Lwow, F
Scientific reports. 2019;(1):16026
Abstract
The observed increase in morbidity and mortality due to tobacco-related cancers, especially those in the respiratory system and esophagus, is becoming a public health challenge. Smoking cigarettes is one of the main risk factors predisposing individuals to many types of cancers. The aim of this study was to determine the role of select vitamin D receptor (VDR) gene polymorphisms as risk factors in tobacco-related cancers. The MEDLINE and ResearchGate databases were used to search for articles up to June 2017, and 12 articles including 26 studies concerning FokI, ApaI, TaqI and BsmI polymorphisms and lung, neck, head, esophageal and oral cancers were chosen. In total, 5 113 cases and 5 657 controls were included in the pooled analysis. We found a significant relationship between tobacco-related cancers and the occurrence of the "t" allele in the TaqI polymorphism of VDR. The occurrence of the "t" allele reduced the risk of tobacco-related cancers by 17% (OR = 0.83, 0.72-0.96 95% CI, p-value = 0.0114). Our analysis revealed that there is a correlation between the TaqI polymorphism of VDR and the risk of tobacco-related cancers.
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4.
The association between vitamin D receptor gene polymorphism and susceptibility to hypertension: a meta-analysis.
Zhu, YB, Li, ZQ, Ding, N, Yi, HL
European review for medical and pharmacological sciences. 2019;(20):9066-9074
Abstract
OBJECTIVE Current studies reporting the association between VDR polymorphisms and susceptibility to hypertension are controversial. This meta-analysis aims to obtain a precise correlation estimate between VDR polymorphisms and susceptibility to hypertension. MATERIALS AND METHODS Relevant studies were searched in PubMed, Web of Science, CNRI, Wanfang, and VIP using the keywords as "Vitamin D receptor, hypertension", "Vitamin D receptor polymorphism, hypertension", and "VDR, hypertension". ORs and corresponding 95%CI of eligible studies were calculated using RevMan5.3 and STATA12.0. RESULTS Seven independent studies reporting the association between VDR gene polymorphisms and hypertension were enrolled. VDR rs1544410 (BsmI) was associated with susceptibility to hypertension. The frequency of VDR BsmI AA genotype decreased in hypertension patients compared with healthy controls. The population carrying VDR BsmI AA genotype had lower susceptibility to hypertension relative to those carrying GA or GG genotype (OR = 0.69, 95% CI = 0.54-0.89, p = 0.005). Meanwhile, the frequency of A allele was higher in the case group than that of control group (OR = 0.83, 95% CI = 0.69-0.99, p = 0.04). No significant correlation was found between VDR FokI or VDR ApaI with susceptibility to hypertension. CONCLUSIONS VDR BsmI gene polymorphism is closely related to the susceptibility to hypertension.
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5.
Role of Vitamin D Receptor Gene Polymorphisms on the Susceptibility to Periodontitis: A Meta-Analysis of a Controversial Issue.
Wan, QS, Li, L, Yang, SK, Liu, ZL, Song, N
Genetic testing and molecular biomarkers. 2019;(9):618-633
Abstract
Background: To assess whether vitamin D receptor (VDR) gene polymorphisms influence the susceptibility to periodontitis. Methods: We retrieved 34 relevant studies, comprising a total of 3848 subjects suffering from periodontitis and 3470 controls for this meta-analysis. The pooled data were analyzed using STATA software. Results: Among all ethnic groups examined, the VDR BsmI polymorphism was associated with periodontitis under the recessive model (odds ratio [OR] = 0.722, 95% confidence interval [CI]: 0.532-0.980, p = 0.037). There was also a link between the VDR FokI polymorphism and periodontitis in the overall population (dominant model: OR = 1.459, 95% CI: 1.050-2.028, p = 0.025 and allelic model: OR = 1.386, 95% CI: 1.026-1.874, p = 0.034) and in Chinese participants (dominant model: OR = 1.813, 95% CI: 1.185-2.774, p = 0.006; allelic model: OR = 1.602, 95% CI: 1.044-2.459, p = 0.031) when stratified by race. The FokI variant was also correlated with aggressive periodontitis (AP) (dominant model: OR = 2.204, 95% CI: 1.148-4.231, p = 0.018; allelic model: OR = 2.017, 95% CI: 1.365-2.980, p = 0.000; and recessive model: OR = 2.903, 95% CI: 1.520-5.542, p = 0.001). We also showed a correlation between the VDR TaqI variant and periodontitis susceptibility in Caucasian populations (dominant model: OR = 0.525, 95% CI: 0.318-0.866, p = 0.012). The results revealed that there was no relationship between the VDR ApaI gene polymorphism and periodontitis. Conclusions: There was a link between the VDR BsmI and FokI gene polymorphisms and periodontitis in the overall population. In addition, the FokI polymorphism was correlated with AP. There was a link between the TaqI polymorphism and periodontitis in the Caucasian population. The VDR Apal variant, however, was not correlated with periodontitis.
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6.
Association of Methylenetetrahydrofolate Reductase, Vitamin D Receptor, and Interleukin-16 Gene Polymorphisms With Renal Cell Carcinoma Risk.
Zhou, T, Li, H, Xie, WJ, Zhong, Z, Zhong, H, Lin, ZJ
Technology in cancer research & treatment. 2019;:1533033819859413
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Abstract
In this meta-analysis, we investigated the association of methylenetetrahydrofolate reductase, vitamin D receptor, and interleukin-16 gene polymorphisms with the risk of renal cell carcinoma. We searched the PubMed and Cochrane Library databases up to July 1, 2017, and included 12 eligible case-control studies in our analysis. The vitamin D receptor ApaI A allele, ApaI AA and aa genotypes, BsmI B allele, and Fok1 FF genotype were all associated with the risk of renal cell carcinoma in Asian populations. However, methylenetetrahydrofolate reductase (rs1801133 and rs1801131), vitamin D receptor (TaqI and Fok1), and interleukin-16 (rs4778889 and rs11556218) gene polymorphisms were not associated with the risk of renal cell carcinoma. Our study indicates that the vitamin D receptor ApaI A allele, ApaI AA and aa genotypes, BsmI B allele, and Fok1 FF genotype are associated with renal cell carcinoma risk.
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7.
The Impact of Vitamin D Receptor Gene Polymorphisms on the Susceptibility of Diabetic Vascular Complications: A Meta-Analysis.
Song, N, Yang, S, Wang, YY, Tang, SQ, Zhu, YQ, Dai, Q, Zhang, H
Genetic testing and molecular biomarkers. 2019;(8):533-556
Abstract
Background: To determine whether vitamin D receptor (VDR) gene polymorphisms are correlated with susceptibility to diabetic vascular complications. Methods: We included all eligible studies, and used Stata12.0 to calculate the pooled results. Results: Eight thousand eleven diabetic patients and 1635 normal controls from 27 studies were included. Our results showed that there was no correlation between VDR gene TaqI variants and diabetic nephropathy (DN) or diabetic retinopathy (DR) susceptibility. In comparison with diabetic patients without DN, there was a link between the VDR gene ApaI variant and DN susceptibility under allelic model (p = 0.029) in all populations. In addition, the VDR gene BsmI variant correlated with DN under both dominant (p = 0.005) and allelic (p = 0.003) models in Asian populations. The VDR gene FokI variant was also correlated with DN susceptibility under the recessive model (p = 0.027) in the Asian subgroup. In comparison with diabetic patients without DR, we identified a link between the VDR gene ApaI variant and DR susceptibility under the dominant model (p = 0.034) in all populations. Also, the VDR gene FokI variant was correlated with DR under the recessive (p = 0.016), the allelic (p = 0.001), and the dominant (p < 0.001) models in all populations. When compared with healthy controls, the VDR gene BsmI variant was associated with DR under the additive (p = 0.014), the allelic (p = 0.033), and the dominant (p < 0.001) models in Indian populations. Conclusions: The VDR gene BsmI, ApaI, and FokI gene variants are associated with DN and DR susceptibility. No association was found between the VDR gene TaqI gene variants and diabetic vascular complications.
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8.
Association of vitamin D receptor polymorphisms and nephrolithiasis: A meta-analysis.
González-Castro, TB, Blachman-Braun, R, Hernández-Díaz, Y, Tovilla-Zárate, CA, Pérez-Hernández, N, Moscardi, PRM, Alam, A, Borgonio-Cuadra, VM, Reyes-López, PA, Juárez-Rojop, IE, et al
Gene. 2019;:143936
Abstract
Nephrolithiasis is a complex disease in which its pathophysiology is strongly influenced by genetics. Polymorphisms of the vitamin D receptor (VDR) gene have been reported to be associated with the development of kidney stones which in most cases are composed predominantly of calcium salts. For the purpose of this study, we performed a systematic review and meta-analysis to analyze the association of BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) polymorphisms with nephrolithiasis. A systematic search was performed up to June 2018 using PubMed, Embase and ISI Web of Knowledge databases. The keywords used for the search were "vitamin D receptor or VDR" and "polymorphisms or SNPs" combined with "urolithiasis or nephrolithiasis". A meta-analysis was performed with the results of the selected and included studies. After analyzing 23 publications, we observed that BsmI polymorphism (rs1544410) has a protective association against nephrolithiasis (Allelic model: OR = 0.84, CI 95% 0.73-0.96, Z p-value 0.015; homozygous model: OR = 0.72, CI 95% 0.54-0.97, Z p-value 0.033). Furthermore, we observed that FokI polymorphism (rs2228570) has a decreased risk of nephrolithiasis in the heterozygous model in the presence of heterogeneity (OR = 0.69, CI 95% 0.48-0.99, Z p-value 0.044), as well as in the absence of heterogeneity (OR = 0.81, CI 95% 0.66-0.99, Z p-value 0.045). Additionally, TaqI polymorphism (rs731236) was associated with a decreased risk of nephrolithiasis in the heterozygous model (OR = 0.77, CI 95% 0.63-0.94, Z p-value 0.010), and no overall association was observed with ApaI polymorphism (rs7975232). This meta-analysis provided comprehensive evidence that VDR polymorphisms are associated with upper urinary tract stones incidence and the genetic variants we studied provide protection against nephrolithiasis.
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9.
Associations between vitamin D receptor genetic variants and periodontitis: a meta-analysis.
Yu, X, Zong, X, Pan, Y
Acta odontologica Scandinavica. 2019;(7):484-494
Abstract
Objective: Numerous studies already investigated potential associations between vitamin D receptor (VDR) genetic variants and periodontitis. However, the results of these studies were not consistent. Previous studies failed to reach a consensus regarding associations between VDR variants and periodontitis partially because of their relatively small sample sizes. Thus, we performed the present meta-analysis to explore the relationship between VDR variants and periodontitis in a larger pooled sample size. Material and methods: Systematic literature research was conducted in PubMed, Web of Science, Embase and CNKI to identify eligible case-control studies on associations between VDR variants and periodontitis. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the strength of associations in all possible genetic models, and p values ≤.05 were considered to be statistically significant. Results: Totally 30 studies were enrolled for analyses. Pooled analyses suggested that VDR rs2228570 variant was significantly associated with the susceptibility to periodontitis under dominant genetic model in the overall population (p = .03, OR = 0.82, 95%CI: 0.69-0.98, I2 = 0). Further subgroup analyses yielded similar positive results for rs2228570 variant in East Asians and patients with chronic periodontitis. Nevertheless, no any other positive findings were observed in overall and subgroup analyses. Conclusions: Our meta-analysis supported that VDR rs2228570 variant might serve as a genetic biomarker of periodontitis. However, further well-designed studies are still warranted to confirm our findings.
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10.
The effects of serum levels, and alterations in the genes of binding protein and receptor of vitamin D on gastric cancer.
Durak, Ş, Gheybi, A, Demirkol, Ş, Arıkan, S, Zeybek, ŞÜ, Akyüz, F, Yaylım, İ, Küçükhüseyin, Ö
Molecular biology reports. 2019;(6):6413-6420
Abstract
Due to many biological cell functions of vitamin D including regulation of cell survival, proliferation and differentiation, the metabolism of itself gains importance in the development of several types of cancer. This case-control study was designed to evaluate the risk of gastric cancer development in terms of VDR rs2228570 & rs731236, and VDBP rs7041 polymorphisms, and serum levels of vitamin D. The study consists of 77 gastric cancer patients and 84 healthy individuals. VDR and VDBP gene polymorphisms and vitamin D levels were determined by using PCR-RFLP and HPLC methods. The distribution of VDR or VDBP gene variants were not different in study groups. The serum level of 25-hydroxyvitamin D was significantly lower in gastric cancer patients versus controls (16 ± 6 → 11 ± 6 ng/ml) in which male patients have higher levels than females. Although the whole study population lacks normal levels of 25-hydroxyvitamin D, it was found that the risk of the development of gastric cancer was approximately fourfold higher in cases with severe vitamin D (< 10 ng/ml) deficiency. Our results indicate that VDR rs731236 & rs2228570 or VDBP rs7041 polymorphisms were not risk factors for the development of gastric cancer individually, however, lower serum levels of vitamin D may be a contributory risk for both predisposition and development of gastric cancer.