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1.
Vitamin D receptor (VDR) gene polymorphism and risk of rheumatoid arthritis (RA): systematic review and meta-analysis.
Bagheri-Hosseinabadi, Z, Imani, D, Yousefi, H, Abbasifard, M
Clinical rheumatology. 2020;(12):3555-3569
Abstract
Vitamin D is involved in immune system modulation as well as in calcium and bone homeostasis, hence plays a role in rheumatoid arthritis (RA) etiopathogenesis. A bulk of studies in different populations have assessed the association between the vitamin D receptor (VDR) gene polymorphisms and the risk of RA, reporting conflicting results. Therefore, we designed a meta-analysis to comprehensively evaluate the association of VDR gene polymorphisms and RA risk. All potential studies reporting the association between VDR gene polymorphisms and susceptibility to RA published till February 2020 were retrieved through systematic search of database, including Scopus and MEDLINE. Strength of pooled association was determined through calculating the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analysis was performed by stratifying the studies by population type. This meta-analysis included 23 eligible studies (21 articles) overall. We noticed that FokI SNP had a significant protective association with susceptibility to RA in the overall analysis as well as in Europeans and Asians. TaqI SNP decreased the RA risk in Africans and Arabs, but not in the overall analysis. Likewise, BsmI SNP and RA risk in the overall population analysis was not significant. Interestingly, BsmI polymorphism increased RA risk in Africans. This meta-analysis offers a significant association between VDR gene polymorphism and susceptibility to RA in both overall and ethnic-specific analysis. However, different polymorphisms acted inversely in increasing or decreasing RA risk in different populations.
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2.
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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3.
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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4.
Vitamin D Receptor Polymorphisms Associated with Autism Spectrum Disorder.
Guerini, FR, Bolognesi, E, Chiappedi, M, Mensi, MM, Fumagalli, O, Rogantini, C, Zanzottera, M, Ghezzo, A, Zanette, M, Agliardi, C, et al
Autism research : official journal of the International Society for Autism Research. 2020;(5):680-690
Abstract
Vitamin D is endowed with a number of biological properties, including down-regulation of inflammation, and might contribute to the pathogenesis of autism spectrum disorders (ASD). Vitamin D binds to the vitamin D Receptor (VDR); the biological activity of the ensuing complex depends on VDR FokI, BsmI, ApaI, and TaqI gene polymorphisms. We evaluated such Single Nucletoide Polymorphismsm (SNPs) in a cohort of 100 Italian families with ASD children. FokI genotype distribution was skewed in ASD children compared with their healthy sibs (Pc = 0.03 2 df) and to a group of 170 Italian healthy women (HC) (Pc = 0.04 2 df). FokI genotype and allelic distribution skewing were also observed in mothers of ASD children compared to HC (Pc = 0.04 2 df). Both Transmission Disequilibrium Test for single loci and haplotype analysis distribution revealed a major FokI (C) allele-mediated protective effect, which was more frequently transmitted (73%) than not transmitted to healthy sibs (P = 0.02). A protective FokI-, BsmI-, ApaI-, and TaqI (CCAG) haplotype was more frequently carried by healthy sibs than by ASD children (P = 1 × 10-4 ; OR: 0.1, 95% CI: 0.03-0.4) too. Finally, a strong gene-dose association of FokI (T) allele with both higher Childhood Autism Rating Scale score (Pc = 0.01) and, particularly, with hyperactivity behavior (Pc = 0.006) emerged in ASD children. Because the protein produced by the FokI (T) allele is transcriptionally less active than that produced by the FokI (C) allele, the reduced biological activity of the vitamin D/VDR complex prevalent in ASD could favor ASD- and maternal immune activation- associated inflammation. Vitamin D supplementation might be useful in preventative and rehabilitation protocols for ASD. Autism Res 2020, 13: 680-690. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY Vitamin D deficiency and Vitamin D receptor (VDR) polymorphisms are associated with structural and functional brain abnormalities and behavioral disorders. We analyzed the association of VDR gene polymorphisms in a cohort of 100 Italian families with ASD children. A strong correlation between one of the VDR polymorphisms and hyperactivity behavior was evidenced in ASD children. In healthy mothers, the same VDR polymorphism was also correlated with an increased risk of giving birth to children with ASD.
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5.
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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6.
Vitamin D receptor ApaI, TaqI, BsmI, and FokI polymorphisms and psoriasis susceptibility: an updated meta-analysis.
Lee, YH
Clinical and experimental dermatology. 2019;(5):498-505
Abstract
BACKGROUND Vitamin D is considered a regulator of the immune system, and its polymorphisms have been associated with psoriasis in some but not all reports. AIM: To explore whether vitamin D receptor (VDR) polymorphisms are associated with susceptibility to psoriasis. METHODS Meta-analyses were conducted to determine the associations between psoriasis and the VDR ApaI, TaqI, BsmI and FokI polymorphisms in all participants, and stratified by ethnic group. RESULTS In total, 16 studies on VDR polymorphisms and psoriasis were included in this meta-analysis, which involved 2086 patients and 2182 controls. The meta-analysis indicated an association between psoriasis and the VDR TaqI TT genotype in Caucasian (OR = 1.29, 95% CI = 1.00-1.66, P < 0.05), but not in Asian (OR = 1.32, 95% CI = 0.89-1.96, P = 0.16) populations. However, no association was found between psoriasis and the VDR TaqI polymorphism using dominant, allele contrast or homozygous contrast models. No association was found between psoriasis and either the VDR ApaI, BsmI or FokI polymorphisms by meta-analyses of the allele contrast, recessive, or dominant models or homozygous contrast models in the overall, Caucasian or Asian populations. CONCLUSION This meta-analysis showed that polymorphisms in VDR ApaI, BsmI and FokI are not associated with psoriasis susceptibility in overall, Caucasian or Asian populations. However, the VDR TaqI polymorphism is associated with psoriasis susceptibility in Caucasian populations.
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7.
Associations between vitamin D receptor genetic variants and tuberculosis: a meta-analysis.
Xu, X, Shen, M
Innate immunity. 2019;(5):305-313
Abstract
We performed a meta-analysis to evaluate potential associations between vitamin D receptor ( VDR) genetic variants and tuberculosis (TB). Systematic literature research was conducted in PubMed, Web of Science, and Embase. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to estimate strength of associations in all possible genetic models, and P values ≤ 0.05 were considered to be statistically significant. In total, 42 studies were enrolled for analyses. Pooled overall analyses suggested that VDR rs1544410 (dominant model: P = 0.02; allele model: P = 0.03) and rs731236 (dominant model: P = 0.04; recessive model: P = 0.02; allele model: P = 0.01) variants were significantly associated with TB. Further subgroup analyses by ethnicity revealed that rs1544410 (dominant and allele models) and rs731236 (dominant, recessive, and allele models) variants were both significantly associated with TB in South Asians. When we stratified data by type of disease, positive results were detected for rs7975232 variant in EPTB (dominant, recessive, over-dominant, and allele models) subgroup, and for rs2228570 variant in PTB (dominant, recessive, and allele models) and EPTB (dominant, recessive, over-dominant, and allele models) subgroups. Our meta-analysis supported that rs7975232, rs1544410, rs2228570, and rs731236 variants might serve as genetic biomarkers of certain types of TB.
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8.
Extra-Skeletal Effects of Vitamin D.
Marino, R, Misra, M
Nutrients. 2019;(7)
Abstract
The vitamin D receptor is expressed in multiple cells of the body (other than osteoblasts), including beta cells and cells involved in immune modulation (such as mononuclear cells, and activated T and B lymphocytes), and most organs in the body including the brain, heart, skin, gonads, prostate, breast, and gut. Consequently, the extra-skeletal impact of vitamin D deficiency has been an active area of research. While epidemiological and case-control studies have often suggested a link between vitamin D deficiency and conditions such as type 1 and type 2 diabetes, connective tissue disorders, inflammatory bowel disorders, chronic hepatitis, food allergies, asthma and respiratory infections, and cancer, interventional studies for the most part have failed to confirm a causative link. This review examines available evidence to date for the extra-skeletal effects of vitamin D deficiency, with a focus on randomized controlled trials and meta-analyses.
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9.
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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10.
Mechanisms of action of vitamin D in colon cancer.
Ferrer-Mayorga, G, Larriba, MJ, Crespo, P, Muñoz, A
The Journal of steroid biochemistry and molecular biology. 2019;:1-6
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Abstract
Colorectal cancer (CRC) is the neoplasia that is most frequently associated with vitamin D deficiency in epidemiological and observational studies in terms of incidence and mortality. Many mechanistic studies show that the active vitamin D metabolite (1α,25-dihydroxyvitamin D3 or calcitriol) inhibits proliferation and promotes epithelial differentiation of human colon carcinoma cell lines that express vitamin D receptor (VDR) via the regulation of a high number of genes. A key action underlining this effect is the multilevel inhibition of the Wnt/β-catenin signaling pathway, whose abnormal activation in colon epithelial cells initiates and promotes CRC. Recently, our group has shown that calcitriol modulates gene expression and inhibits protumoral properties of patient-derived colon cancer-associated fibroblasts (CAFs). Accordingly, high VDR expression in tumor stromal fibroblasts is associated with longer survival of CRC patients. Moreover, many types of immune cells express VDR and are regulated by calcitriol, which probably contributes to its action against CRC. Given the role attributed to the intestinal microbiota in CRC and the finding that it is altered by vitamin D deficiency, an indirect antitumoral effect of calcitriol is also plausible at this level. In summary, calcitriol has an array of potential protective effects against CRC by acting on carcinoma cells, CAFs, immune cells and probably also the gut microbiota.