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1.
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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2.
Vitamin D Receptor ApaI (rs7975232) Polymorphism Confers Decreased Risk of Pulmonary Tuberculosis in Overall and African Population, but not in Asians: Evidence from a Meta-analysis.
Areeshi, MY, Mandal, RK, Wahid, M, Dar, SA, Jawed, A, Lohani, M, Abdallah, AMA, Khan, S, Panda, AK, Mishra, BN, et al
Annals of clinical and laboratory science. 2017;(5):628-637
Abstract
GOALS The involvement of the VDR ApaI gene polymorphism in the development of pulmonary tuberculosis (PTB) has been reported by numerous published studies and yielded inconsistent results. The present meta-analysis evaluated the association of VDR ApaI polymorphism and risk of PTB occurrence. PROCEDURES PubMed (Medline), EMBASE and Google Scholar web-databases were searched and a meta-analysis was performed by calculating the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS This meta-analysis included a total of 14 eligible studies comprising of 1958 confirmed PTB cases and 2938 controls. We observed decreased risk of PTB in allelic (a vs. A: p=0.003; OR=0.873, 95% CI=0.798 to 0.955), homozygous (aa vs. AA: p=0.006; OR=0.761, 95% CI=0.626 to 0.924), dominant (aa+Aa vs. AA: p=0.039; OR=0.874, 95% CI=0.769 to 0.993) and recessive (aa vs. AA+Aa: p=0.025; OR=0.819, 95% CI=0.688 to 0.975) genetic models. During subgroup analysis, allele (a vs. A: p=0.005; OR=0.846, 95% CI=0.753 to 0.951), homozygous (aa vs. AA: p=0.002; OR=0.662, 95% CI=0.513 to 0.854) and recessive genetic models (aa vs. AA+Aa: p=0.003; OR=0.709, 95% CI=0.566 to 0.889) demonstrated decreased PTB risk in African population. However, no significant association was observed in Asian population. CONCLUSION In conclusion, VDR ApaI polymorphism is significantly associated with decreased risk of PTB for in overall and African population, but not in Asians.
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3.
Pharmacodynamic Effects of Sucroferric Oxyhydroxide and Sevelamer Carbonate on Vitamin D Receptor Agonist Bioactivity in Dialysis Patients.
Sprague, SM, Covic, AC, Floege, J, Ketteler, M, Botha, J, Chong, EM, Rastogi, A
American journal of nephrology. 2016;(2):104-12
Abstract
BACKGROUND Many patients with chronic kidney disease are prescribed vitamin D receptor agonists (VDRAs) for the management of secondary hyperparathyroidism. Oral phosphate binders may interact with, and potentially reduce the therapeutic activity of, oral VDRAs. This post hoc analysis of a Phase 3 study evaluated the pharmacodynamic effects of the iron-based phosphate binder sucroferric oxyhydroxide (SFOH) and sevelamer (SEV) carbonate on VDRA activity in dialysis patients. METHODS One thousand and fifty nine patients were randomized to SFOH 1.0-3.0 g/day (n = 710) or SEV 2.4-14.4 g/day (n = 349) for up to 52 weeks. Potential interactions of SFOH and SEV with VDRAs were assessed using serum intact parathyroid hormone (iPTH) concentrations as a pharmacodynamic biomarker. Three populations of SFOH- and SEV-treated patients were analyzed: Population 1 (n = 187), patients taking concomitant stable doses of oral VDRAs only; Population 2 (n = 250), patients taking no concomitant VDRAs; Population 3 (n = 68), patients taking concomitant stable doses of intravenous paricalcitol only. Populations were compared using a mixed-effects model to obtain the least squares mean change in iPTH from baseline to Week 52. Differences between treatment groups were also compared. RESULTS In Population 1, iPTH decreased from baseline to Week 52 in the SFOH group (-25.3 pg/ml) but increased in the SEV group (89.8 pg/ml) (p = 0.02). In Population 2, iPTH increased to a similar extent in both treatment groups. In Population 3, iPTH concentrations in both treatment groups decreased to a similar degree (-29.6 and -11.4 pg/ml for SFOH and SEV, respectively; p = 0.87). CONCLUSIONS In contrast with SEV, SFOH did not appear to impact the iPTH-lowering effect of oral VDRAs.
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4.
Genetic Variations in the Vitamin D Receptor Predict Type 2 Diabetes and Myocardial Infarction in a Community-Based Population: The Tromsø Study.
Zostautiene, I, Jorde, R, Schirmer, H, Mathiesen, EB, Njølstad, I, Løchen, ML, Wilsgaard, T, Joakimsen, RM, Kamycheva, E
PloS one. 2015;(12):e0145359
Abstract
BACKGROUND Though the associations between low serum 25-hydroxyvitamin D (25(OH)D) levels and health outcomes such as type 2 diabetes (T2D), myocardial infarction (MI), cancer, and mortality are well-studied, the effect of supplementation with vitamin D is uncertain. This may be related to genetic differences. Thus, rs7968585, a single nucleotide polymorphism (SNP) of the vitamin D receptor (VDR), has recently been reported as a predictor of composite health outcome. We therefore aimed to evaluate whether rs7968585 predicts separate clinical outcomes such as T2D, MI, cancer, and mortality in a community-based Norwegian population. METHODS AND FINDINGS Measurements and DNA were obtained from the participants in the Tromsø Study in 1994-1995, registered with the outcomes of interest and a randomly selected control group. The impact of the rs7968585 genotypes was evaluated with Cox proportional hazards. A total of 8,461 subjects were included among whom 1,054 subjects were registered with T2D, 2,287 with MI, 3,166 with cancer, and 4,336 with death. Mean follow-up time from birth was 60.8 years for T2D and MI, 61.2 years for cancer, while mean follow-up time from examination date was 16.5 years for survival. Mean serum 25(OH)D levels did not differ across the rs7968585 genotypes. With the major homozygote genotype as reference, the minor homozygote subjects had hazard ratios of 1.25 (95% CI 1.05-1.49) for T2D and 1.14 (1.02-1.28) for MI (P = 0.011 and 0.023, respectively, without the Bonferroni correction). No significant interaction between serum 25(OH)D status and the rs7968585 genotype was found for any of the endpoints. CONCLUSIONS The VDR-related SNP rs7968585 minor allele is a significant and positive predictor for T2D and possibly for MI. Since the functional mechanism of this SNP is not yet understood, and the association with T2D is reported for the first time, confirmatory studies are needed.
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5.
The association between FOK-I vitamin D receptor gene polymorphisms and bone mineral density in patients with systemic lupus erythematosus.
Jacobs, J, Voskuyl, AE, Korswagen, LA, Theunissen, R, Cohen Tervaert, JW, Bultink, IE
Clinical and experimental rheumatology. 2015;(5):765
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6.
Effect of VDRA on survival in incident hemodialysis patients: results of the FARO-2 observational study.
Messa, P, Cozzolino, M, Brancaccio, D, Cannella, G, Malberti, F, Costanzo, AM, di Luzio Paparatti, U, Festa, V, Gualberti, G, Mazzaferro, S, et al
BMC nephrology. 2015;:11
Abstract
BACKGROUND Mortality rate among patients with stage five chronic kidney disease (CKD) maintained on hemodialysis (HD) is high. Although evidence suggests that use of Vitamin D Receptor Activators (VDRA) in CKD patients increases survival, few studies have examined the effect of VDRA in incident HD patients. The FARO-2 study evaluated the clinical outcome of VDRA therapy on mortality in incident HD patients. METHODS FARO-2 was a longitudinal epidemiological study performed on 568 incident HD patients followed prospectively from 26 dialysis centers over a 3-year period. Data were collected every 6 months using a questionnaire, obtaining clinical, biochemical and therapeutic parameters. Kaplan-Meier curves and Cox proportional hazard regression models were used to determine cumulative probability of time-to-death and adjusted hazard ratios. RESULTS 568 patients (68% male) with an average age of 65.5 years were followed up. Mean dialysis duration at study entry was 3 months. VDRA use increased from 46% at 6 months to 54.7% at 36 months of follow-up (p = 0.08). No difference was observed in the presence of comorbid diseases at baseline in patients with and without VDRA therapy. Cumulative probability of survival at 24 months was 74.5% (95% CI: 70.2-78.3). Patients receiving VDRA therapy showed a significant increase in survival at 24 months (80.7%; 95% CI: 75.7-84.8) compared to those without (63.3%; 95% CI: 54.8-70.7, p <0.01). The presence of vascular disease, decreased hemoglobin, increased P and lack of VDRA treatment were significantly associated with an increased risk of mortality. Lack of VDRA treatment still remained significant as a predictor of mortality after adjusting for levels of PTH, P and Ca (HR = 2.16, 95% CI: 1.09-4.30, p = 0.03). CONCLUSIONS Findings from FARO-2 indicate that in incident HD patients VDRA therapy was associated with increased survival.
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7.
Association of vitamin D receptor gene polymorphisms with asthma risk: systematic review and updated meta-analysis of case-control studies.
Tizaoui, K, Berraies, A, Hamdi, B, Kaabachi, W, Hamzaoui, K, Hamzaoui, A
Lung. 2014;(6):955-65
Abstract
BACKGROUND The association between vitamin D receptor (VDR) polymorphisms and asthma risk has been inconsistently investigated, but published studies demonstrated conflicting results. The aim of the current study was to investigate the impact of TaqI, BsmI, ApaI, and FokI VDR polymorphisms on asthma disease by using a meta-analysis approach. METHODS Following the preferred reporting items for systematic reviews and meta-analyses guidelines, a systematic search and meta-analysis of the literature were conducted. Subgroup analyses were performed to detect potential sources of heterogeneity from selected study characteristics. RESULTS A total of 2,097 cases and 1,968 controls in eight case-control studies were included in meta-analyses. A significant association was found between TaqI polymorphisms and asthma risk [OR 1.488 (95 % CI 1.019-2.174); P = 0.040] in a codominant model. In the same way, BsmI was significantly associated with asthma risk [OR 2.017 (95 % CI 1.236-3.851); P = 0.017] in the codominant model. The homozygote BB BsmI genotype was found to confer significant asthma risk. FokI polymorphism was marginally associated with asthma risk [OR 1.187 (95 % CI 0.975-1.446); P = 0.088] in the codominant model. In contrast, no significant association was found between ApaI polymorphism and asthma risk. Subgroup analyses revealed that gender and age modified significantly the association between FokI polymorphisms and asthma risk (P = 0.035 and 0.013, respectively). Publication year and serum 25(OH) D level tended, marginally, to moderate the association between FokI polymorphism and asthma risk. CONCLUSION TaqI, BsmI, and FokI VDR polymorphisms contribute to asthma susceptibility. The association between FokI polymorphism and asthma risk is influenced by study characteristics.
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8.
Association between vitamin D receptor gene BsmI, FokI, ApaI and TaqI polymorphisms and the risk of systemic lupus erythematosus: a meta-analysis.
Mao, S, Huang, S
Rheumatology international. 2014;(3):381-8
Abstract
Association studies of vitamin D receptor (VDR) gene polymorphisms and the risk of systemic lupus erythematosus (SLE) have yielded conflicting results in different backgrounds. We aimed to evaluate the association between VDR gene polymorphisms and SLE risk. A predefined electronic databases search was performed to identify eligible studies that were related to the association of VDR gene BsmI, FokI, ApaI or TaqI polymorphism with SLE risk. Either a fixed-effects model, or in the presence of heterogeneity, a random-effects model was used to calculate the pooled odds ratios (ORs) and its corresponding 95% confidence interval (CI). A total of 11 studies with 1,621 cases and 1,883 controls were included in this meta-analysis. BsmI B allele was associated with the onset of SLE for overall populations (OR 1.726, 95% CI 1.214-2.455) and Asians (OR 1.952, 95% CI 1.135-3.355). FokI FF genotype was correlated with the susceptibility of SLE for Asians (OR 1.469, 95% CI 1.005-2.148). FokI T/C and TaqI polymorphisms were not associated with SLE risk for Caucasians. There was no significant association between ApaI polymorphism and SLE risk for overall populations, Asians and Caucasians. No evidence of publication bias was observed. In conclusion, BsmI B allele may be a risk factor for SLE onset among overall populations and Asians, and FokI FF genotype is a risk factor for SLE susceptibility in Asians. However, more studies should be performed in the future.
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9.
Vitamin D receptor gene polymorphisms on the risk of tuberculosis, a meta-analysis of 29 case-control studies.
Chen, C, Liu, Q, Zhu, L, Yang, H, Lu, W
PloS one. 2013;(12):e83843
Abstract
The relationship of four potentially functional polymorphisms of the vitamin D receptor (VDR) gene, ApaI, BsmI, FokI and TaqI , with tuberculosis susceptibility were considered. The aim of this meta-analysis was to explore the association between the four polymorphisms and tuberculosis risk in different ethnic backgrounds. Eligible case-control studies that were catalogued before April 1(st) 2013 were enrolled, and the heterogeneity between the studies was evaluated using a χ(2) based Q-test. Fixed and random effect models were built to evaluate the association of the four polymorphisms with the risk of tuberculosis, and the association between the four polymorphisms and tuberculosis was expressed as the odds ratio (OR) and 95% confidence interval (CI). Finally, twenty nine qualified studies were enrolled for this meta-analysis that included 6179 tuberculosis cases and 6585 healthy controls. The variant homozygote genotype of the FokI polymorphism was associated with a significantly increased risk of tuberculosis when compared to the heterozygote and wild type homozygote genotypes in the Chinese population (ff vs. Ff+FF: OR(recessive) =1.97, 95%CI: 1.32-2.93, P(bonferroni) =0.0032; heterogeneity test: χ(2)=0.24, P=0.62). For European subjects, the homozygote and heterozygote genotypes of the BsmI polymorphism were associated with a significantly decreased risk of tuberculosis when compared to the wild type homozygote (bb+Bb vs. BB: OR(dominant) =0.41, 95%CI, 0.22-0.76, P(bonferroni) =0.02; heterogeneity test: χ(2)=2.59, P=0.11). Based on the above results, we conclude that variants of the VDR gene that are homozygous for the FokI polymorphism might be more susceptible to tuberculosis in Chinese. Furthermore, larger sample studies are warranted to confirm the protective effects of BsmI variants on tuberculosis in the Europeans.
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10.
Association between vitamin D receptor polymorphisms and periodontitis: a meta-analysis.
Chen, LL, Li, H, Zhang, PP, Wang, SM
Journal of periodontology. 2012;(9):1095-103
Abstract
BACKGROUND The purpose of the meta-analysis is to explore the association between vitamin D receptor polymorphisms (including four gene loci: Taq-I, Bsm-I, Apa-I, and Fok-I) for susceptibility to periodontitis (either chronic [CP] or aggressive [AP]). Up to now, there has been only one systematic review focusing on this topic. We obtained some different findings compared with the previously published literature. METHODS Nineteen case-control studies were identified through a search of multiple electronic databases (from January 1, 1999 to June 30, 2011). The pooled odds ratios (ORs) and 95% confidence intervals (CIs) using codominant, dominant, and recessive genetic models from meta-analysis were the main outcome measure. The Harbord test was used to detect the publication bias for each group. RESULTS Eighteen identified articles met the eligibility criteria. Through overall analyses, no statistical association was found between polymorphisms of the four gene loci and periodontitis. However, based on subgroup analyses, a significant association between the Taq-I variants and CP rather than AP was shown in Asians (OR = 0.590; 95% CI = 0.425, 0.818) but not in whites (OR = 0.823; 95% CI = 0.637, 1.063). No statistically significant association was found between polymorphisms of Bsm-I and Apa-I with either AP or CP. The Fok-I polymorphism showed a statistical association with AP (OR = 1.583; 95% CI = 1.157, 2.166) instead of CP (OR = 1.081; 95% CI = 0.638, 1.830) in Asians. CONCLUSIONS The results of the present meta-analysis indicate the following: 1) the mutant allele t of the Taq-I locus may be a protective factor for CP but not for AP in Asians, although this was not true in whites; 2) the mutant allele F of the Fok-I locus appeared to be a risk factor for AP rather than CP in Asians; and 3) Bsm-I and Apa-I polymorphisms were found to have no significant associations with susceptibility to periodontitis (CP/AP).