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1.
Vitamin D receptor gene polymorphism and susceptibility to asthma: Meta-analysis based on 17 case-control studies.
Makoui, MH, Imani, D, Motallebnezhad, M, Azimi, M, Razi, B
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2020;(1):57-69
Abstract
BACKGROUND During the last decade, several studies have evaluated the potential association between vitamin D receptor (VDR) gene polymorphism and susceptibility to asthma. In spite of valuable findings, the results are still contradictory. Therefore, a comprehensive meta-analysis not only solves discrepancies but provides a clue for future projects. OBJECTIVE This meta-analysis was performed to identify whether VDR gene polymorphisms (FokI (rs2228570) or TaqI (rs731236) or BsmI (rs1544410) or ApaI (rs7975232)) play a role in the risk of asthma. METHODS Electronic search of Web of Science, Scopus, and PubMed databases were systematically conducted from their inception until June 2019, to identify all published studies. Eligibility of the studies was confirmed by precise inclusion and exclusion criteria, and the resultant studies were analyzed. RESULTS A total of 17 studies concerning VDR gene polymorphisms and asthma risk were included in this meta-analysis. The results of pooled analysis indicated a statistically significant association between FokI SNP (dominant model [OR = 0.78, 95% CI, 0.62-0.98, random effect model] and allelic model [OR = 0.81, 95% CI, 0.67-0.98, random effect model]) and TaqI SNP (homozygote contract model [OR = 0.70, 95% CI, 0.54-0.89]) with asthma risk. Moreover, subgroup analysis showed that ethnicity influences asthma risk in Asian, African, and American populations. The sensitivity analyses confirmed the stability of the results. CONCLUSION This meta-analysis suggests that VDR gene polymorphism is associated with the risk of asthma.
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2.
VDR Agonists Increase Sensitivity of MCF-7 and BT-474 Breast Cancer Cells to 5 FU.
Klopotowska, D, Matuszyk, J
Anticancer research. 2020;(2):837-840
Abstract
BACKGROUND/AIM: The study aimed to test the potential for increasing the antiproliferative activity of 5-fluorouracil against breast cancer cells of various molecular subtypes by vitamin D receptor (VDR) agonists, calcitriol and tacalcitol, used at a low concentration of 10 nM. MATERIALS AND METHODS Calcitriol and tacalcitol were used to increase the antiproliferative effect of 5-fluorouracil against the following human breast cancer cell lines: MCF-7, T47D, BT-474 (luminal); JIMT-1, SKBR-3 (HER2-enriched); MDA-MB-231 (triple-negative/basal-B), and non-malignant MCF-10A breast epithelial cells. RESULTS Both calcitriol and tacalcitol significantly increased the sensitivity of MCF-7 and BT-474 cells to the antiproliferative effect of 5-fluorouracil, while no increase in the sensitivity of MDA-MB-231 cells to 5-fluorouracil treatment was observed. CONCLUSION The VDR agonist used at the relatively low concentration of 10 nM may increase the sensitivity of breast cancer cells, at least of the luminal subtype, to the antiproliferative effect of 5-fluorouracil.
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3.
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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4.
Prognostic role of vitamin D receptor in breast cancer: a systematic review and meta-analysis.
Xu, H, Liu, Z, Shi, H, Wang, C
BMC cancer. 2020;(1):1051
Abstract
BACKGROUND A higher vitamin D intake improves the prognosis of early stage breast cancer (BC) patients. We hypothesized that vitamin D intake should refer to vitamin D receptor (VDR) expression. In order to prove this hypothesis, we first intend to evaluate the correlation between VDR expression and prognosis of BC patients using meta-analysis. METHODS Literatures from PubMed, Embase, and the Cochrane Library (last update by May 20, 2020) were retrieved to find studies assessing the prognostic role of VDR in BC. The hazard ratios (HRs) for patients' survival were extracted for pooled analyses. Subgroup analysis, sensitivity analysis and meta-regression were performed to explore the sources of heterogeneity. RESULTS Seven articles containing eight studies with 2503 patients were enrolled. The results from the pooled analyses showed that the VDR expression generally had no relationship with BC patients' overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and progression-free survival (PFS) (P > 0.05). Because only the number of studies exploring the relationship between VDR expression and OS is greater than five and there is heterogeneity, we explored the sources of heterogeneity of these studies. Subgroup analyses showed that the VDR expression in the nucleus had no relationship with OS, but high total VDR expression in the nucleus and cytoplasm was related to a better OS (pooled HR = 0.41; 95% CI = 0.18-0.95; P = 0.038). In addition, in subgroup of studies using cut-off values other than 'immunoreactive score (IRS)>5' and 'IRS > 25', high VDR expression was associated with a better OS (pooled HR = 0.47; 95% CI = 0.30-0.74; P = 0.001). Sensitivity analysis showed that the result pattern was not obviously affected by any single study. Meta-regression showed that the source of heterogeneity was not country (P = 0.657), pathological type (P = 0.614), molecular type (P = 0.423), staining location (P = 0.481), or cut-off value (P = 0.509). CONCLUSIONS The protein expression level of VDR in entire BC cells evaluated by immunohistochemistry is related to the OS of BC patients. It is expected that a more individualized vitamin D intake and a more accurate prognosis assessment can be recommended for BC patients based on the VDR expression. Of course, more preclinical and clinical studies are needed.
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5.
The Correlation Between Vitamin D Receptor (VDR) Gene Polymorphisms and Autism: A Meta-analysis.
Yang, H, Wu, X
Journal of molecular neuroscience : MN. 2020;(2):260-268
Abstract
Vitamin D receptor (VDR) polymorphisms are risk factors for autism. We performed a systematic meta-analysis to explore the relationship between VDR gene polymorphisms and autism. A literature review of articles from Pubmed, Embase, the Cochrane Library, and Springer was conducted up to January 28, 2019. The association between SNPs and autism was calculated using pooled odd ratios (ORs) and 95% confidence intervals (CIs). Additionally, tests for heterogeneity, publication bias, and sensitivity were conducted. Six eligible studies with a total of 2001 participants (1045 cases and 956 controls) were included. Meta-analysis indicated that the "C" allele of the rs731236 gene, including C vs. T (OR = 1.3254, 95% CI = 1.0897-1.6122), CC vs. TT (OR = 2.0871, 95% CI = 1.3395-3.2519), and CC vs. TT + CT (OR = 1.9610, 95% CI = 1.2985-2.9615), might be a risk factor for autism. Moreover, the "G" allele of rs7975232 (G vs. T: OR = 0.8228, 95% CI = 0.6814-0.9934) was associated with a protective effect against the development of autism. No significant differences were found in the allele frequencies of rs11568820, rs1544410, and rs2228570 in the cases and controls. This meta-analysis revealed that both VDR rs731236 and rs7975232 were significantly associated with autism, whereas VDR rs11568820, rs1544410, and rs2228570 might not be correlated with the incidence of autism.
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6.
A comparative analysis of the efficacy and safety of paricalcitol versus other vitamin D receptor activators in patients undergoing hemodialysis: A systematic review and meta-analysis of 15 randomized controlled trials.
Geng, X, Shi, E, Wang, S, Song, Y
PloS one. 2020;(5):e0233705
Abstract
Paricalcitol, a new vitamin D receptor activator (VDRA), is reported to be more effective than other VDRAs in reducing calcium and phosphorus levels in patients undergoing hemodialysis. However, the efficacy and safety of paricalcitol remain controversial. This analysis compares paricalcitol with other VDRAs in patients undergoing hemodialysis. We searched the Cochrane Library, PubMed, EMBASE, Web of Science, and CNKI up to April 22, 2019. Standardized mean difference (SMD), risk ratio (RR) and 95% confidence interval (CI) values were estimated to compare the outcomes of the groups. Two reviewers extracted data and assessed trial quality independently. All statistical analyses were performed using the standard statistical procedures of RevMan 5.2 and Stata 12.0. Fifteen studies (N = 110,544) were included in this meta-analysis. Of these studies, 11 were randomized controlled trials (RCTs) and 4 were non-randomized studies of interventions (NRSIs). Patients receiving paricalcitol experienced better overall survival (OS) than patients receiving other VDRAs, with a pooled hazard ratio of 0.86 (95% CI 0.80-0.91; P < 0.00001). Intact parathyroid hormone (iPTH) levels were significantly reduced in the paricalcitol group compared to the group receiving other VDRAs, with a pooled SMD of -0.53 (95% CI -0.89- -0.16; P = 0.004). There was a significant increase in serum calcium levels from baseline in the paricalcitol group compared to the other VDRAs group when limiting the analysis to RCTs, with a pooled SMD of 2.14 (95% CI 0.90-3.38; P = 0.0007). Changes in serum calcium levels were significantly lower in the paricalcitol group when the analysis was limited to NRSIs, with a pooled SMD of -0.85 (95% CI -1.34--0.35; P = 0.0008). The NSRI analysis also showed a significant reduction in serum phosphorus levels in the paricalcitol group, with a pooled SMD of -0.57 (95% CI -1.00--0.13; P = 0.01). No significant differences were observed in the incidence of hypercalcemia, hyperphosphatemia, or adverse events. Generally, paricalcitol seems superior to other VDRAs in reducing mortality and iPTH levels in patients undergoing hemodialysis. However, the comparative effectiveness of paricalcitol in reducing serum calcium and phosphorus levels needs further exploration. No significant difference was found in the rate of adverse events.
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7.
Vitamin D receptor gene polymorphisms and susceptibility to urolithiasis: a meta-regression and meta-analysis.
Imani, D, Razi, B, Khosrojerdi, A, Lorian, K, Motallebnezhad, M, Rezaei, R, Aslani, S
BMC nephrology. 2020;(1):263
Abstract
BACKGROUND The currently available data with respect to the association between vitamin D receptor (VDR) gene polymorphism and risk to urolithiasis are inconclusive and inconsistent. Hence, an exhaustive meta-analysis can solve the discrepancies and provide a hint for upcoming investigations. Herein, a meta-analysis was carried out to attain a conclusive estimate of the association between VDR gene single nucleotide polymorphisms (SNPs) and urolithiasis risk. METHODS The major databases, including ISI Web of science, Scopus, and PubMed/MEDLINE were searched systematically from until June 2020 to retrieve all relevant studies. Association between VDR gene polymorphisms, including FokI (rs2228570), TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232), and urolithiasis risk was evaluated using pooled odds ratio (OR) and their corresponding 95% confidence interval (CI). Additionally, to seek for the potential source of heterogeneity, meta-regression analyses were exerted. RESULTS Literature search led to finally finding of 33 studies evaluating the VDR gene SNPs and urolithiasis risk. It was observed that none of the four SNPs were significantly associated with urolithiasis predisposition. However, subgroup analysis confirmed higher risk of urolithiasis in East-Asian and Caucasian population with ApaI and TaqI gene polymorphism. The analyses of sensitivity acknowledged the results stability. CONCLUSION Although this meta-analysis did not support the association of FokI, TaqI, BsmI, and ApaI in the overall polled analysis, it suggests that ApaI and TaqI SNPs is associated with increased risk of urolithiasis in East-Asian and Caucasians populations.
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8.
Vitamin D receptor gene polymorphisms in ocular surface squamous cell neoplasms.
Ismayilova, N, Palamar, M, Onay, H, Ceylan, EI, Atik, T, Akalin, T, Yagci, A
European journal of ophthalmology. 2020;(5):901-907
Abstract
PURPOSE To investigate vitamin D receptor polymorphisms in ocular surface squamous cell neoplasm and to evaluate the relationship between the identified polymorphisms and susceptibility to ocular surface squamous cell neoplasm and the clinical course. MATERIALS AND METHODS A totala of 70 patients with ocular surface squamous cell neoplasm (study group) and 75 healthy age and gender-matched individuals (control group) were included in the study. Vitamin D receptor FokI and BsmI polymorphisms were examined. The relationships between histopathological diagnosis, recurrence rates, tumor stage, and identified polymorphisms were investigated. RESULTS Histopathologically, 43 of the cases were squamous cell carcinoma and 27 of the cases were conjunctival intraepithelial neoplasia. The frequency of FokI (FF, Ff, ff) and BsmI (BB, Bb, bb) polymorphism genotype of vitamin D receptor gene were similar in the groups. The frequency of polymorphism (heterozygous or homozygous) for BsmI (Bb and bb) was significantly higher (p = 0.046) in the study group, while no difference was found between the groups in terms of polymorphic carriers (heterozygous or homozygous) for FokI. There was no correlation between tumor stage, recurrence-polymorphism frequency, and patient age-polymorphism frequency. CONCLUSION It is known that active vitamin D inhibits the growth of cancer cells by binding to vitamin D receptor with regulation of genes responsible for cell proliferation. The presence of BsmI polymorphism in vitamin D receptor, in particular bb genotype and b allele, appears to be associated with the susceptibility of ocular surface squamous cell neoplasm. BsmI gene polymorphisms of vitamin D receptor might play an effective role in the formation, progression, and in the course of ocular surface squamous cell neoplasm.
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9.
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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10.
Vitamin D receptor gene polymorphisms and the risk of the type 1 diabetes: a meta-regression and updated meta-analysis.
Zhai, N, Bidares, R, Makoui, MH, Aslani, S, Mohammadi, P, Razi, B, Imani, D, Yazdchi, M, Mikaeili, H
BMC endocrine disorders. 2020;(1):121
Abstract
BACKGROUND The association between the polymorphisms in the vitamin D receptor (VDR) gene and the risk of type 1 diabetes mellitus (T1DM) has been evaluated in several studies. However, the findings were inconclusive. Thus, we conducted a meta-analysis to comprehensively evaluate the effect of VDR gene polymorphisms on the risk of T1DM. METHODS All relevant studies reporting the association between VDR gene polymorphisms and susceptibility to T1DM published up to May 2020 were identified by comprehensive systematic database search in ISI Web of Science, Scopus, and PubMed/MEDLINE. Strength of association were assessed by calculating of pooled odds ratios (ORs) and 95% confidence intervals (CIs). The methodological quality of each study was assessed according to the Newcastle-Ottawa Scale. To find the potential sources of heterogeneity, meta-regression and subgroup analysis were also performed. RESULTS A total of 39 case-control studies were included in this meta-analysis. The results of overall population rejected any significant association between VDR gene polymorphisms and T1DM risk. However, the pooled results of subgroup analysis revealed significant negative and positive associations between FokI and BsmI polymorphisms and T1DM in Africans and Americans, respectively. CONCLUSIONS This meta-analysis suggested a significant association between VDR gene polymorphism and T1DM susceptibility in ethnic-specific analysis.