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1.
Vitamin D/VDR in the pathogenesis of intervertebral disc degeneration: Does autophagy play a role?
Lan, T, Shen, Z, Hu, Z, Yan, B
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112739
Abstract
To date, the underlying mechanisms involved intervertebral disc degeneration (IDD) remain unclear, which has hindered the development of molecular biological therapy for IDD. Autophagy is vital for intracellular quality control and metabolic balance in intervertebral disc cells. Hence, autophagy homeostasis is important. Emerging evidence has implicated vitamin D (VD) and the vitamin D receptor (VDR) in IDD progression because of their effects on different autophagy steps. However, the results of clinical trials in which VD supplementation was assessed as a treatment for IDD are controversial. Furthermore, experimental studies on the interplay between VD/VDR and autophagy are still in their infancy. In view of the significance of the crosstalk between VD/VDR and autophagy components, this review focuses on the latest research on VD/VDR modulation in autophagy and investigates the possible regulatory mechanisms. This article will deepen our understanding of the relationship between VD/VDR and autophagy and suggests novel strategies for IDD prevention and treatment.
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2.
Vitamin D Receptor (VDR) Gene Polymorphisms and Risk of Coronary Artery Disease (CAD): Systematic Review and Meta-analysis.
Tabaei, S, Motallebnezhad, M, Tabaee, SS
Biochemical genetics. 2021;(4):813-836
Abstract
Several studies have noted that vitamin D receptor (VDR) gene polymorphisms are involved in the susceptibility to Coronary artery disease (CAD). Nonetheless, the results have been inconclusive. Here, we performed the most up-to-date analysis of the association between VDR gene polymorphisms and risk of CAD. We conducted a comprehensive systematic search in the major electronic database, including Scopus and PubMed to look up for relevant studies evaluating the association between the VDR gene FokI (rs2228570), TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232) polymorphisms and susceptibility to CAD published before December 2019. The level of association between VDR gene polymorphisms and susceptibility to CAD in the polled analysis was calculated by odds ratio (OR) and the corresponding 95% confidence interval (CI). We found 14 articles containing 20,398 cases and 9371 controls. The analysis revealed that all genetic models in the FokI SNP were associated with increased risk of CAD. Furthermore, for the ApaI SNP, except recessive model, all other genetic models significantly increased the risk of CAD in the overall analysis. In addition, it was divulged that both FokI and ApaI SNPs were involved in increasing the risk of CAD in Asians and Europeans in a number of models. FokI and ApaI polymorphisms may confer a susceptibility genetic risk factor for development of CAD, particularly in the Asian population.
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3.
Polymorphisms of Vitamin D Receptor and the Effect on Metabolic and Endocrine Abnormalities in Polycystic Ovary Syndrome: A Review.
Vulcan, T, Filip, GA, Lenghel, LM, Suciu, T, Ilut, P, Procopciuc, LM
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2021;(10):645-653
Abstract
Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorder in women of reproductive age. Vitamin D and its receptor are thought to play an important role in PCOS susceptibility, although the impact of vitamin D receptor (VDR) polymorphisms on the hormonal and metabolic profile is still controversial. A literature search in PubMed and Embase was performed up to September 2020 for case-control studies in women suffering from PCOS, with outcome related to VDR polymorphisms effect on metabolic/endocrine disturbances. We have found 16 eligible studies including 2566 women with PCOS and 2430 controls. ApaI polymorphism seemed to be associated with hyperandrogenism in both Asian and Caucasian population. FokI variant was correlated with metabolic/endocrine parameters especially in Asian population, while a relation between Cdx2 genotypes and insulin sensitivity was observed in both ethnicities. VDR polymorphisms have an important role in PCOS development and related hormonal and metabolic abnormalities. Few case-control studies analysed the interaction between VDR variants and metabolic/endocrine parameters with the majority of the articles focused on the Asian region. Further research on various ethnic populations with larger sample size are still needed for a definitive conclusion, in order to allow early diagnosis and prevention of PCOS comorbidities.
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4.
Vitamin D and Genetic Susceptibility to Multiple Sclerosis.
Scazzone, C, Agnello, L, Bivona, G, Lo Sasso, B, Ciaccio, M
Biochemical genetics. 2021;(1):1-30
Abstract
Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system (CNS), resulting from the interaction among genetic, epigenetic, and environmental factors. Vitamin D is a secosteroid, and its circulating levels are influenced by environment and genetics. In the last decades, research data on the association between MS and vitamin D status led to hypothesize a possible role for hypovitaminosis D as a risk factor for MS. Some gene variants encoding proteins involved in vitamin D metabolism, transport, and function, which are responsible for vitamin D status alterations, have been related to MS susceptibility. This review explores the current literature on the influence of vitamin D-related genes in MS susceptibility, reporting all single-nucleotide polymorphisms (SNPs) investigated to date in 12 vitamin D pathway genes. Among all, the gene codifying vitamin D receptor (VDR) is the most studied. The association between VDR SNPs and MS risk has been reported by many Authors, with a few studies producing opposite results. Other vitamin D-related genes (including DHCR7/NADSYN1, CYP2R1, CYP27A1, CYP3A4, CYP27B1, CYP24A1, Megalin-DAB2-Cubilin, FGF-23, and Klotho) have been less investigated and achieved more conflicting evidence. Taken together, findings from the studies reviewed cannot clarify whether and to what extent vitamin D-related gene variants can influence MS risk.
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5.
Roles of Vitamin D in Reproductive Systems and Assisted Reproductive Technology.
Chen, Y, Zhi, X
Endocrinology. 2020;(4)
Abstract
Vitamin D, an essential steroid hormone in the human body, plays an important role in not only the regulation of calcium and phosphorus metabolism, but also in various physiological processes, such as cell differentiation and apoptosis, inflammation, and insulin resistance. Vitamin D receptors are widely distributed in male and female reproductive systems, suggesting that vitamin D is essential for fertility. Because vitamin D deficiency is highly prevalent around the world, this review aims to discuss the potential functions of vitamin D in male and female reproductive systems and the associations between vitamin D and assisted reproductive technology (ART) outcomes. Vitamin D is involved in many physiological reproductive processes, including steroidogenesis, spermatogenesis, and acrosome reaction. It is correlated with sperm quality, ovarian reserve, polycystic ovarian syndrome, and endometriosis, among others. Controversial clinical findings on vitamin D levels and ART outcomes were revealed in this review, and demonstrations of efficacy for human fertility in randomized controlled trials of vitamin D supplementation are notably lacking. Thus, further studies are highly required involving molecular mechanisms among different species and human populations, as well as randomized controlled trials.
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6.
Vitamin D in trichology: a comprehensive review of the role of vitamin D and its receptor in hair and scalp disorders.
Damiani, G, Conic, R, Orlando, G, Zampetti, A, Marinello, E, Piai, M, Linder, MD
Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia. 2020;(2):190-197
Abstract
Vitamin D plays an important role in maintaining the homeostasis of various biological systems. Beside its well-known function in calcium and phosphate metabolism, it plays a major role in pathophysiology of skin and adnexa. Indeed, vitamin D, through its receptor (VDR), decreases keratinocyte proliferation, improves their differentiation and modulates both cutaneous innate (antimicrobial activity and antigen presentation) and adaptative immunity (T and B lymphocyte function). The maintenance of normal hair is dependant on the integrity of the dermis, epidermis and hair cycles. Beside its effect on epidermal differentiation, VDR plays a vital role in preserving the hair follicle integrity. While the relevance of VDR has been fully elucidated, the real value of vitamin D in the hair follicle cycle still remains uncertain. To date, results in literature remain contradicting and far from definitive; still, the role of vitamin D in the various forms of human alopecia is likely to be significant. The aim of this article is to review evidence about the role of vitamin D and its receptor in trichology, with a focus on scarring and non-scarring alopecia and in particular on the potential therapeutic use of Vitamin D for hair and scalp disorders.
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7.
Gut instincts: vitamin D/vitamin D receptor and microbiome in neurodevelopment disorders.
Ogbu, D, Xia, E, Sun, J
Open biology. 2020;(7):200063
Abstract
The gut microbiome regulates a relationship with the brain known as the gut-microbiota-brain (GMB) axis. This interaction is influenced by immune cells, microbial metabolites and neurotransmitters. Recent findings show gut dysbiosis is prevalent in autism spectrum disorder (ASD) as well as attention deficit hyperactivity disorder (ADHD). There are previously established negative correlations among vitamin D, vitamin D receptor (VDR) levels and severity of ASD as well as ADHD. Both vitamin D and VDR are known to regulate homeostasis in the brain and the intestinal microbiome. This review summarizes the growing relationship between vitamin D/VDR signalling and the GMB axis in ASD and ADHD. We focus on current publications and summarize the progress of GMB in neurodevelopmental disorders, describe effects and mechanisms of vitamin D/VDR in regulating the microbiome and synoptically highlight the potential applications of targeting vitamin D/VDR signalling in neurodevelopment disorders.
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8.
The Vitamin D Receptor as Tumor Suppressor in Skin.
Bikle, DD
Advances in experimental medicine and biology. 2020;:285-306
Abstract
Cutaneous malignancies including melanomas and keratinocyte carcinomas (KC) are the most common types of cancer, occurring at a rate of over one million per year in the United States. KC, which include both basal cell carcinomas and squamous cell carcinomas, are substantially more common than melanomas and form the subject of this chapter. Ultraviolet radiation (UVR), both UVB and UVA, as occurs with sunlight exposure is generally regarded as causal for these malignancies, but UVB is also required for vitamin D synthesis in the skin. Keratinocytes are the major cell in the epidermis. These cells not only produce vitamin D but contain the enzymatic machinery to metabolize vitamin D to its active metabolite, 1,25(OH)2D, and express the receptor for this metabolite, the vitamin D receptor (VDR). This allows the cell to respond to the 1,25(OH)2D that it produces. Based on our own data and that reported in the literature, we conclude that vitamin D signaling in the skin suppresses UVR-induced epidermal tumor formation. In this chapter we focus on four mechanisms by which vitamin D signaling suppresses tumor formation. They are inhibition of proliferation/stimulation of differentiation with discussion of the roles of hedgehog, Wnt/β-catenin, and hyaluronan/CD44 pathways in mediating vitamin D regulation of proliferation/differentiation, regulation of the balance between oncogenic and tumor suppressor long noncoding RNAs, immune regulation, and promotion of DNA damage repair (DDR).
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9.
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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10.
Association of Vitamin D Receptor Gene Polymorphism With the Risk of Nephrolithiasis.
Yang, SK, Song, N, Wang, YY, Li, AM, Liu, J, Deng, F, Zhan, M, Zhang, W, Han, YC, Zhang, H
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2019;(5):425-436
Abstract
This study aimed to explore the relationship between vitamin D receptor (VDR) gene polymorphisms and the risk of nephrolithiasis. All relevant trials were searched from multiple databases according to predefined criteria, the pooled OR and corresponding 95% CI were analyzed using Stata software. Seventeen studies involving 2441 cases and 2296 controls were included. The pooled analysis showed that VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with nephrolithiasis susceptibility either in Asian and in Caucasians populations. VDR TaqI gene polymorphism was associated with nephrolithiasis in the overall populations (T vs. t: OR = 0.84, 95% CI: 0.73-0.95, P = 0.006; TT vs. Tt + tt: OR = 0.79, 95% CI: 0.66-0.95, P = 0.010). In Asian population, VDR TaqI gene polymorphism also was associated with nephrolithiasis susceptibility (TT vs. Tt + tt: OR = 0.72, 95% CI: 0.55-0.93, P = 0.012; Tt vs. TT + tt: OR = 1.43, 95% CI: 1.00-2.05, P = 0.048). But TaqI gene polymorphism was not associated with nephrolithiasis risk in Caucasian populations (T vs. t: OR = 0.85, 95% CI: 0.72-1.00, P = 0.051; TT vs. Tt + tt: OR = 0.87, 95% CI: 0.68-1.10, P = 0.245; tt vs. Tt + TT: OR = 1.32, 95% CI: 0.86-2.01, P = 0.206; Tt vs. TT+ tt: OR = 0.98, 95% CI: 0.70-1.38, P = 0.931). VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with the risk of nephrolithiasis either in Asian and Caucasians populations, but VDR TaqI gene polymorphism was associated with nephrolithiasis in the Asian subjects.