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Associations between vitamin D receptor gene polymorphisms and spinal degenerative disease: evidence from a meta-analysis based on 35 case-control studies.
Gao, S, Xun, C, Xu, T, Cao, R, Zhang, J, Liang, W, Sheng, W
Clinical neurology and neurosurgery. 2021;:106325
Abstract
OBJECTIVE Dozens of reports on the associations of vitamin D receptor (VDR) gene polymorphisms and susceptibility to spinal degenerative disease (SDD) were conducted with inconsistent findings. This study aimed to elucidate the associations through a meta-analysis approach. METHODS Databases of PubMed, EMBASE, Web of Science, CNKI, and Wanfang were searched until July 10, 2020. Study quality was evaluated by using Newcastle-Ottawa Scale (NOS). Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to evaluate the associations under allelic model (1 vs. 2), homozygous model (11 vs. 22), heterozygous model (12 vs. 22), dominant model (11 + 12 vs. 22), and recessive model (11 vs. 12 + 22). RESULTS A total of 5021 cases and 5746 controls from 35 studies were eligible to this meta-analysis. According to NOS, the included studies were in excellent quality. In the overall population, the pooled data indicated that ApaI was associated with a reduced SDD susceptibility (AA vs. Aa + aa, OR = 0.83, 95%CI 0.71 - 0.96, P = 0.010). But the association was not observed in FokI, TaqI, and BsmI polymorphisms. Subgroup analysis suggested that TaqI polymorphism was correlated to an elevated SDD risk in Asians (TT + Tt vs. tt, OR = 2.55, 95%CI 1.90 - 3.44, P < 0.001). CONCLUSION The present study indicates that ApaI polymorphism may contribute to a reduced risk to SDD in the overall population, and TaqI polymorphism confers an elevated susceptibility to SDD in Asians. While, BsmI and FokI polymorphisms appear to have no significant association with SDD.
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A systematic review and meta-analysis of the associations of vitamin D receptor genetic variants with two types of most common neurodegenerative disorders.
Geng, J, Zhang, J, Yao, F, Liu, X, Liu, J, Huang, Y
Aging clinical and experimental research. 2020;(1):21-27
Abstract
BACKGROUND Whether vitamin D receptor (VDR) genetic variants influence individual susceptibility to neurodegenerative disorders remains controversial. AIMS This meta-analysis was conducted to analyze correlations of VDR genetic variants with two types of most common neurodegenerative disorders, Parkinson's disease (PD) and Alzheimer's disease (AD). METHODS Systematic literature research of PubMed and Embase was performed to identify eligible articles. Q test and I2 statistic were employed to decide whether pooled analyses would be performed with random-effect models (REMs) or fixed-effect models (FEMs). All statistical analyses were conducted with Review Manager. RESULTS Totally sixteen studies were enrolled for analyses. Among these eligible studies, ten studies were about PD (2356 cases and 2815 controls) and six studies were about AD (1256 cases and 1205 controls). Pooled overall analyses suggested that VDR rs7975232 (additive model: p = 0.03, OR = 1.19, 95% CI 1.01-1.39) and rs2228570 (recessive model: p < 0.008, OR = 1.26, 95% CI 1.06-1.50; allele model: p < 0.001, OR = 0.80, 95% CI 0.71-0.91) variants were significantly correlated with PD, and VDR rs731236 (dominant model: p = 0.003, OR = 0.70, 95% CI 0.56-0.89; additive model: p = 0.02, OR = 1.32, 95% CI 1.06-1.66; allele model: p = 0.02, OR = 0.82, 95% CI 0.69-0.96) variant was significantly correlated with AD. Further subgroup analyses by ethnicity revealed that the positive results were mainly driven by the Asians, whereas no significant associations were observed in Caucasians. CONCLUSION Our meta-analysis suggested that VDR rs7975232 and rs2228570 variants might serve as genetic biomarkers of PD, whereas VDR rs731236 variant might serve as a genetic biomarker of AD.
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A meta-analysis of the relationship between vitamin D receptor gene ApaI polymorphisms and polycystic ovary syndrome.
Liang, F, Ren, N, Zhang, H, Zhang, J, Wu, Q, Song, R, Shi, Z, Zhang, Z, Wang, K
Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2019;(2):255-262
Abstract
BACKGROUND Emerging evidence from pre-clinical and clinical studies has shown that vitamin D (VD) plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS). Potentially functional ApaI polymorphism of vitamin D receptor (VDR) gene has been implicated in PCOS risk, but individually published studies have yielded inconclusive results. OBJECTIVES Studies on the associations of VDR gene polymorphisms with PCOS susceptibility reported conflicting results. The objective of this study was to perform a systematic meta-analysis to clarify this issue. MATERIAL AND METHODS We searched for all publications regarding the associations mentioned above in PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) databases updated up to April 2017. A meta-analysis of the overall odds ratios (ORs) with 95% confidence interval (CI) was calculated with the fixed or random effect model. RESULTS A total of 7 studies fulfilling the inclusion criteria were included in this meta-analysis (1,350 cases and 960 controls). Pooled ORs showed a significant association between ApaI polymorphism and PCOS risk in all 4 genetic models. Subgroup analysis by ethnicity showed that ApaI polymorphism was associated with the risk of PCOS in Asians (aa vs AA: OR = 1.54, 95% CI = 1.04-2.28, p = 0.03). However, ApaI polymorphism (a vs A: OR = 1.34, 95% CI = 1.00-1.79, p = 0.02; aa+Aa vs AA: OR = 1.36, 95% CI = 1.04-1.79, p = 0.03) was associated with the risk of PCOS in Caucasians. CONCLUSIONS Our meta-analysis demonstrated that PCOS risk was significantly associated with VDR gene ApaI polymorphism. However, due to the relatively small sample size in this meta-analysis, further studies with a larger sample size should be conducted to confirm the findings.
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Do genetic polymorphisms of the vitamin D receptor contribute to breast/ovarian cancer? A systematic review and network meta-analysis.
Li, J, Li, B, Jiang, Q, Zhang, Y, Liu, A, Wang, H, Zhang, J, Qin, Q, Hong, Z, Li, BA
Gene. 2018;:211-227
Abstract
BACKGROUND To identify the most suitable genetic model for detecting the risk of breast cancer (BC)/ovarian cancer (OC) in specific populations. METHODS Databases were searched for related studies published up to October 2017. First, VDR genetic polymorphisms were compared in patients with and without cancer. Second, a network meta-analysis was used to reveal the relation between VDR genetic polymorphisms with disease outcomes. Subgroup analyses and a meta-regression were performed according to cancer types, ethnicity and genotypic method. The study is registered in PROSPERO with an ID: CRD42017075505. RESULTS Forty-five studies were eligible, which included 65,754 patients and 55 clinical analyses. Of genetic models, results suggested that the recessive model with the CDX2 polymorphism predicted the risk of BC in all cases. The recessive polymorphism model with the rs2228570 (FokI) polymorphism seemed to the best predictor of BC in Caucasian patients, whereas the homozygote model with the CDX2 polymorphism appeared to best predict BC in African-American patients. The homozygote model with the rs2228570 (FokI) polymorphism model appeared to detect the risk of OC in all cases, whereas the heterozygote model with the rs1544410 (BsmI) polymorphism seemed to detect the risk of OC in Caucasian patients. CONCLUSIONS By detecting the risk of BC, the recessive model with the rs2228570 (FokI) polymorphism is likely the best genetic model in Caucasian patients, and the homozygote model with the CDX2 polymorphism appears to be best genetic model in African-American patients. Moreover, for detecting clinical risk of OC, heterozygote models with the rs1544410 (BsmI) polymorphism is likely the best genetic model for detecting the risk of OC in Caucasian patients.
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Role of vitamin D receptor gene polymorphisms in aplastic anemia: a case-control study from China.
Yu, W, Ge, M, Shi, J, Li, X, Zhang, J, Wang, M, Shao, Y, Zheng, Y
International journal of laboratory hematology. 2016;(3):273-83
Abstract
INTRODUCTION Vitamin D receptor (VDR) gene and its polymorphisms are highlighted as candidate components for susceptibility to various autoimmune diseases. The aim of this study was to investigate the role of VDR polymorphisms (rs2228570, rs1544410, rs7975232, and rs731236) in aplastic anemia (AA). METHODS In this case-control study, the genotyping of VDR rs1544410 (c.1024 + 283G>A), rs7975232 (c.1025-49G>T), and rs731236 (c.1056T>C) polymorphisms was conducted using polymerase chain reaction (PCR)-ligase detection reaction, while the genotyping of rs2228570 (c.2T>C) was detected by PCR-restriction fragment length polymorphism. RESULTS The frequencies of GG genotype and G allele of rs1544410 were significantly higher in patients with AA than in controls. Further analysis indicated that rs1544410 and rs7975232 polymorphisms were correlated with the risk to nonsevere AA, while rs2228570 was relevant to severe AA. Moreover, TT carriers of rs2228570 were closely associated with a poor response to treatment and a higher risk of myelodysplastic syndrome/acute leukemia transformation, while CT carriers more easily evolved to overt paroxysmal nocturnal hemoglobinuria. CONCLUSIONS VDR polymorphisms may contribute to susceptibility to AA and influence the severity and prognosis of AA in a Chinese population.
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Polymorphisms in the vitamin D receptor gene and type 1 diabetes mellitus risk: an update by meta-analysis.
Zhang, J, Li, W, Liu, J, Wu, W, Ouyang, H, Zhang, Q, Wang, Y, Liu, L, Yang, R, Liu, X, et al
Molecular and cellular endocrinology. 2012;(1):135-42
Abstract
Four well known polymorphisms (BsmI, FokI, ApaI, TaqI) in the VDR gene have been implicated in susceptibility to type 1 diabetes mellitus (T1DM), but the results to date have been inconclusive. The aim of this study was to investigate the association between polymorphisms in the VDR gene and T1DM risk by meta-analysis. A total of 57 case-control studies in 26 published studies were included. The results indicated that the BsmI polymorphism is associated with increased risk of T1DM (BB+Bb vs. bb: OR=1.30, 95% CI=1.03-1.63), while the FokI, ApaI and TaqI polymorphisms were not. In the subgroup analysis by ethnicity, the increased risk of T1DM remained in the Asian subgroup for the BsmI polymorphism; whereas no significant association was found in other populations for other polymorphisms. Results from the current study suggest that the BsmI polymorphism is associated with increased risk of T1DM, especially in Asians. Further studies are needed to confirm our results.