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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.
Impact of Vitamin D Receptor Gene Polymorphism on Systemic Lupus Erythematosus Susceptibility: A Pooled Analysis.
Yang, SK, Liu, N, Zhang, WJ, Song, N, Yang, JP, Zhang, H, Gui, M
Genetic testing and molecular biomarkers. 2022;(4):228-238
Abstract
Background: This study was designed to evaluate the influence of vitamin D receptor (VDR) gene polymorphisms on systemic lupus erythematosus (SLE) susceptibility. Methods: All eligible investigations were identified, the number of the various genotypes in the case and control groups were reviewed. A pooled analysis was performed using the Stata software. The study was carried out according to the Ethics Review Committee of The Third Xiangya Hospital, Central South University. Results: This meta-analysis included 19 studies. In our analysis, the VDR Apal polymorphism was correlated with SLE susceptibility in the overall population (AA vs. aa: odds ratio [OR] = 1.374, 95% confidence interval [CI]: 1.115-1.692, p = 0.003; AA + Aa vs. aa: OR = 1.342, 95% CI: 1.139-1.583, p < 0.01). The VDR Bsml and Apal polymorphisms were correlated with SLE susceptibility in Caucasian subjects (BB vs. Bb + bb: OR = 0.734, 95% CI: 0.593-0.909, p = 0.005; B vs. b: OR = 0.865, 95% CI: 0.760-0.983, p = 0.026; AA vs. aa: OR = 1.329, 95% CI: 1.016-1.740, p = 0.038). The VDR BsmI and FokI polymorphisms were correlated with SLE in African subjects (B vs. b: OR = 1.898, 95% CI: 1.458-2.470, p<0.01; BB + Bb vs. bb: OR = 2.935, 95% CI: 1.944-4.430, p < 0.01; FF vs. Ff + ff: OR = 2.424, 95% CI: 1.673-3.512, p < 0.01; F vs. f: OR = 1.720, 95% CI: 1.417-2.087, p < 0.01; FF vs. ff: OR = 3.154, 95% CI: 2.083-4.774, p < 0.01; FF + Ff vs. ff: OR = 1.803, 95% CI: 1.363-2.384, p < 0.01). In addition, the VDR Apal polymorphism was correlated with SLE in female subjects (AA vs. aa: OR = 1.392, 95% CI: 1.049-1.849, p = 0.022) when stratified by gender. But there was no association between the VDR TaqI polymorphism and SLE susceptibility in our analysis. Conclusions: The VDR Apal polymorphism was associated with SLE susceptibility in general populations; in addition, Apal polymorphism was associated with SLE in female subjects. The VDR Bsml gene polymorphism was correlated with SLE susceptibility in Caucasian and African populations, whereas the VDR FokI polymorphism was correlated with SLE in African populations. But there was no association between the VDR TaqI polymorphism and SLE susceptibility in our analysis.
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3.
Evocalcet with vitamin D receptor activator treatment for secondary hyperparathyroidism.
Shigematsu, T, Asada, S, Endo, Y, Kawata, T, Fukagawa, M, Akizawa, T
PloS one. 2022;(2):e0262829
Abstract
This ad hoc analysis of a previously conducted phase 3 head-to-head comparison study of evocalcet and cinacalcet in secondary hyperparathyroidism patients undergoing maintenance hemodialysis evaluated the efficacy and safety of combined once-daily oral evocalcet and intravenous vitamin D receptor activator treatment stratified by weekly vitamin D receptor activator dose (117, 45, and 91 patients in no, low [< 1.5 μg], and high [≥ 1.5 μg] dose groups, respectively). Effects of vitamin D receptor activator were assessed on the basis of intact parathyroid hormone, corrected calcium, phosphorus, and fibroblast growth factor-23 levels; percent changes from baseline; proportions of patients who achieved target intact parathyroid hormone, corrected calcium, and phosphorus at Weeks 28-30; and adverse drug reactions. Intact parathyroid hormone, corrected calcium, phosphorus, and fibroblast growth factor-23 levels decreased in all groups; phosphorus and fibroblast growth factor-23 levels remained high in the high dose group. In the low and high dose groups, greater proportions of patients achieved the corrected calcium target compared with the no dose group (p = 0.043). Ratios of intact-to-C-terminal fibroblast growth factor-23 decreased in all groups. In low and high dose groups, hypocalcemia was less common than in the no dose group (p = 0.014). Evocalcet with concomitant vitamin D receptor activator demonstrated benefits such that more patients achieved the corrected calcium target and exhibited decreased fibroblast growth factor-23 synthesis; the incidence of hypocalcemia also decreased. Clinical trial registration: ClinicalTrials.gov (NCT02549391) and JAPIC (JapicCTI-153013).
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4.
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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5.
Polymorphisms Contributing to Calcium Status: A Systematic Review.
da Silva Lopes, K, Abe, SK
Nutrients. 2021;(8)
Abstract
This systematic review assessed genotypes and changes in calcium homeostasis. A literature search was performed in EMBASE, Medline and CENTRAL on 7 August 2020 identifying 1012 references. Studies were included with any human population related to the topic of interest, and genetic variations in genes related to calcium metabolism were considered. Two reviewers independently screened references, extracted relevant data and assessed study quality using the Q-Genie tool. Forty-one studies investigating Single Nucleotide Polymorphisms (SNPs) in relation to calcium status were identified. Almost half of the included studies were of good study quality according to the Q-Genie tool. Seventeen studies were cross-sectional, 14 case-control, seven association and three were Mendelian randomization studies. Included studies were conducted in over 18 countries. Participants were mainly adults, while six studies included children and adolescents. Ethnicity was described in 31 studies and half of these included Caucasian participants. Twenty-six independent studies examined the association between calcium and polymorphism in the calcium-sensing receptor (CASR) gene. Five studies assessed the association between polymorphisms of the Vitamin D receptor (VDR) gene and changes in calcium levels or renal excretion. The remaining ten studies investigated calcium homeostasis and other gene polymorphisms such as the CYP24A1 SNP or CLDN14. This study identified several CASR, VDR and other gene SNPs associated with calcium status. However, to provide evidence to guide dietary recommendations, further research is needed to explore the association between common polymorphisms and calcium requirements.
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6.
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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7.
Association between Polymorphisms in Vitamin D Pathway-Related Genes, Vitamin D Status, Muscle Mass and Function: A Systematic Review.
Krasniqi, E, Boshnjaku, A, Wagner, KH, Wessner, B
Nutrients. 2021;(9)
Abstract
An association between vitamin D level and muscle-related traits has been frequently reported. Vitamin D level is dependent on various factors such as sunlight exposure and nutrition. But also on genetic factors. We, therefore, hypothesize that single nucleotide polymorphisms (SNPs) within the vitamin D pathway-related genes could contribute to muscle mass and function via an impact on vitamin D level. However, the integration of studies investigating these issues is still missing. Therefore, this review aimed to systematically identify and summarize the available evidence on the association between SNPs within vitamin D pathway-related genes and vitamin D status as well as various muscle traits in healthy adults. The review has been registered on PROSPERO and was conducted following PRISMA guidelines. In total, 77 studies investigating 497 SNPs in 13 different genes were included, with significant associations being reported for 59 different SNPs. Variations in GC, CYP2R1, VDR, and CYP24A1 genes were reported most frequently, whereby especially SNPs in the GC (rs2282679, rs4588, rs1155563, rs7041) and CYP2R1 genes (rs10741657, rs10766197, rs2060793) were confirmed to be associated with vitamin D level in more than 50% of the respective studies. Various muscle traits have been investigated only in relation to four different vitamin D receptor (VDR) polymorphisms (rs7975232, rs2228570, rs1544410, and rs731236). Interestingly, all of them showed only very low confirmation rates (6-17% of the studies). In conclusion, this systematic review presents one of the most comprehensive updates of the association of SNPs in vitamin D pathway-related genes with vitamin D status and muscle traits in healthy adults. It might be used for selecting candidate SNPs for further studies, but also for personalized strategies in identifying individuals at risk for vitamin D deficiency and eventually for determining a potential response to vitamin D supplementation.
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8.
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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9.
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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10.
Vitamin D Receptor Gene Single Nucleotide Polymorphisms and Association With Vitamin D Levels and Endoscopic Disease Activity in Inflammatory Bowel Disease Patients: A Pilot Study.
Shirwaikar Thomas, A, Criss, ZK, Shroyer, NF, Abraham, BP
Inflammatory bowel diseases. 2021;(8):1263-1269
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Abstract
BACKGROUND Inflammatory bowel diseases (IBDs) comprise a heterogenous group of chronic gastrointestinal disorders that are multifactorial in etiology. Experimental in vitro and in vivo studies suggest that intestinal vitamin D receptor (VDR) signaling plays a role in modulating the immune response in IBD as a cause and/or a consequence of chronic inflammation. AIM: The aim of this study is to study the associations between vitamin D receptor gene single nucleotide polymorphisms(SNPs), vitamin D levels, and endoscopic disease activity in IBD. METHODS This is a cross-sectional analysis of IBD patients who underwent endoscopic evaluation at a tertiary care hospital. Demographic variables, IBD disease type and location, medical therapies, vitamin D levels, and endoscopic disease activity were collected. Colonic biopsies obtained were investigated for the presence of VDR SNPs: ApaI, TaqI, BsmI, FokI, and Tru9I. RESULTS Patients in endoscopic remission had higher vitamin D levels compared with those with inflammation found on endoscopy (P = <0.001). Patients with lower vitamin D levels were homozygous for Fok ancestral alleles (P = 0.0045). With regard to endoscopic disease activity, we found no differences in mutations of any of the VDR SNPs in our sample. CONCLUSIONS The association between the presence of the ancestral FokI and lower vitamin D levels suggests a multifactorial etiology for vitamin D deficiency in IBD. Higher vitamin D levels in those in endoscopic remission compared with lower levels in those with active inflammation suggests that the impact of VDR gene SNP on disease activity may be overcome with replacement therapy.