Vitamin D Receptor (VDR) Gene Polymorphisms and Risk of Coronary Artery Disease (CAD): Systematic Review and Meta-analysis

Tabaei, Samira; Motallebnezhad, Morteza; Tabaee, Seyedeh Samaneh

doi:10.1007/s10528-021-10038-x

Cited by 18 publications

(15 citation statements)

References 45 publications

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“…In the previous meta-analysis [39][40][41], increased risks were found both in rs1544410 and rs731236 polymorphism, which agreed with our results, but decreased risk of rs2228570 was observed in his study. After careful analysis, we supposed the small sample size and different data recruiting methods could contribute to the discrepancy.…”

Section: Plos Onesupporting

confidence: 91%

Four common vitamin D receptor polymorphisms and coronary artery disease susceptibility: A trial sequential analysis

et al. 2022

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Background Studies on the susceptibility of vitamin D receptor (VDR) polymorphisms to coronary artery disease (CAD) reached controversial results. We performed this study for a more accurate evaluation between the VDR polymorphisms and CAD susceptibility. Methods PubMed, Embase, CNKI, Wan Fang, and VIP databases were searched. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to evaluate the associations. Trial sequential analysis (TSA) was introduced to estimate the positive associations. The potential functions of the VDR polymorphisms were analyzed based on the SNPinfo and ENSEMBL databases. Results Thirteen studies were finally included. In the overall analysis, increased CAD risks were observed in the VDR rs1544410 polymorphism and verified by the TSA; for the rs2228570 and rs731236 polymorphisms, significant associations with high heterogeneity were detected; decreased risk was remarkably observed for the rs7975232 polymorphism. In the subgroup analysis, wide associations with reduced heterogeneity were observed in the rs2228570, rs1544410, and rs731236 polymorphisms. The RNAfold analysis indicated the mutant G allele of the rs1544410 polymorphism was easier to disperse from the DNA double helix structure and may have a potential crucial role in the VDR transcription process. Conclusions Our analysis supports the role of the rs1544410 polymorphism in the VDR gene as a risk factor for CAD. The VDR rs2228570 and rs731236 polymorphisms were associated with increased CAD risks in the White population. Restrict decreased CAD risk was firstly discovered in the rs7975232 polymorphism. Limitations Firstly, the language was restricted to English and Chinese, which will cause the limited number of studies included; secondly, other unknown polymorphisms in VDR polymorphisms could also be associated the CAD susceptibility, and more case-control studies with comprehensive clinical outcomes and GWAS studies were required; thirdly, the rs1544410, rs7975232 and rs731236 polymorphism are in strong LD, haploid factors with CAD risk need to be considered; fourthly, the mechanisms of the VDR polymorphism on the VDR gene or RNA or protein were not discussed enough, further mechanistic studies are required; at last, genetic factor was the one side for CAD susceptibility, the interaction between environmental risk factors should be considered.

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Section: Plos Onesupporting

confidence: 91%

Four common vitamin D receptor polymorphisms and coronary artery disease susceptibility: A trial sequential analysis

et al. 2022

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“…Similarly, a study carried out in an Asian population (from India) (292 cases/219 controls) reported a statistically significant association between the T genotype of the VDR FokI polymorphism and susceptibility to developing ischemic cerebrovascular accident (CVA) ( p = 0.01; OR = 1.89; 95% CI = 1.17–3.07; TT vs. CC) [ 49 ]. Furthermore, according to the meta-analysis conducted by Tabaei et al (2021) in Caucasian and Asian populations (3741 cases/1998 controls), the T allele of the VDR FokI SNP was significantly associated with the CAD risk in all genetic models including; dominant model ( p = 0.02; OR = 1.47, 95% CI 1.06–2.03), recessive model ( p < 0.001; OR = 1.39, 95% CI 1.14–1.71), allelic model ( p = 0.01; OR = 1.38, 95% CI 1.08–1.76, p = 0.01), TT vs. CC model ( p = 0.02; OR = 1.58, 95% CI 1.07–2.34), and TC vs. TT model ( p = 0.04; OR = 1.38, 95% CI 1.00–1.92), having a strong significant association for the Asian population but not the Caucasian [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, according to the results of the study carried out by Abouzid et al (2021) they suggest that VDR BsmI -AA genotype is protective of CVD ( p = 0.04) [ 53 ]. Moreover, according to the meta-analysis by Tabaei et al (2021) in Caucasian and Asian populations (6169 cases/2392 controls), VDR ApaI-CC genotype was significantly associated with CAD risk in all genetic models, including: dominant model ( p = 0.002; OR = 1.20, 95% CI 1.07–1.34), allelic model ( p = 0.004; OR = 1.12, 95% CI 1.04–1.21), CC vs. AA model ( p = 0.01; OR = 1.22, 95% CI 1.04–1.44), and AC vs. AA model ( p = 0.007; OR = 1.18, 95% CI 1.05–1.33), other than the recessive model ( p = 0.17; OR = 1.10, 95% CI 0.96–1.27) [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D-Related Single Nucleotide Polymorphisms as Risk Biomarker of Cardiovascular Disease

Rojo

Ramírez

Gálvez-Navas

et al. 2022

IJMS

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Cardiovascular diseases (CVDs) are a group of disorders of the heart and blood vessels. In addition to environmental risk factors, genetic predisposition increases the risk; this includes alterations in the vitamin D receptor gene (VDR). These alterations play a key role in modifying vitamin D uptake, being able to modify its function and increasing susceptibility to cardiovascular disorders. The aim of this study was to evaluate the association of polymorphisms in the VDR gene and risk of CVD in a Caucasian population. A retrospective case-control study was conducted comprising 246 CVD patients and 246 controls of Caucasian origin from Southern Spain. The genetic polymorphisms BsmI (rs1544410), TaqI (rs731236), ApaI (rs7975232), FokI (rs2228570) and Cdx2 (rs11568820) were determined by means of real-time polymerase chain reaction (PCR) for allelic discrimination using TaqMan® probes. The logistic regression analysis adjusted for body mass index and diabetes revealed that the TT genotype was associated with a higher risk of CVD in both the genotypic model (p = 0.0430; OR = 2.30; 95% CI = 1.06–5.37; TT vs. CC) and the recessive model (p = 0.0099; OR = 2.71; 95% CI = 1.31–6.07; TT vs. C). Haplotype analysis revealed that the haplotype GAC (p = 0.047; OR = 0.34; 95% CI = 0.12–0.98) was associated with increased risk of CVD. The VDR polymorphisms FokI (rs2228570) was significantly associated with the development of CVD. No influence was observed of the VDR polymorphisms BsmI (rs1544410), TaqI (rs731236), ApaI (rs7975232) and Cdx2 (rs11568820) on the risk of developing CVD in the patients studied.

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“…This pathway is closely associated with atherosclerosis, and the pro-in ammatory response of monocytes in CAD requires activation of mTOR [36]. Among 'trans' genes, some studies have reported that VDR gene polymorphisms lead to the development and formation of CAD by affecting changes in serum levels of 25(OH) vitamin D. [37,38]. Previous study reported VDR in regulating in ammation through inhibiting the NF-ĸB pathway and activating autophagy [39].…”

Section: Discussionmentioning

confidence: 99%

Epithelial-Mesenchymal Transition-Related lncRNAs And SNAI2 Are Potential Biomarkers in Coronary Artery Disease

Zou

Liu

et al. 2021

Preprint

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BackgroundIncreasing evidence suggests that epithelial-mesenchymal transformation (EMT) is critical in the development of inflammatory response, atherosclerosis, and coronary artery disease (CAD). However, landscapes of EMT-related lncRNAs and their target genes have not been fully established in CAD.MethodsLncRNA and mRNA expression profiles obtained from Gene Expression Omnibus (GEO) database were used to identify the differentially expressed mRNAs (DEGs) and lncRNAs (DElncRNAs) between CAD and normal samples. Based on Pearson correlation analysis to identify the EMT-related lncRNAs, the optimal features were identified by receiver operating characteristic (ROC), the least absolute shrinkage and selection operator (LASSO) regression, Support Vector Machine Reverse Feature Elimination (SVM-RFE) algorithms, and logistic regression models were constructed aiming to distinguish CAD from normal samples. The cis and trans-regulatory networks were constructed based on EMT-related lncRNAs. We further estimated the infiltration of the immune cells in CAD patients with the CIBERSORT algorithm, and the correlation between key genes and infiltrating immune cells was analyzed.ResultsIn this study, a logistic regression model with powerful diagnostic capability was constructed based on a total of eight EMT-related lncRNAs identified by two machine learning methods. Then, results of the immune analysis revealed three significant immune cell subsets (CD8 T cells, monocytes, and NK cells) in CAD patients and found EMT-related lncRNAs were closely correlated with these immune cell subsets. By Pearson correlation analysis we got 34 “cis” and “trans” genes. Among them, SNAI2, an EMT-TF gene, was found in the trans-regulatory network of EMT-related lncRNAs. Further, through logistic regression and analysis of immune cell infiltration, we found SNAI2 was a potential biomarker for the diagnosis of CAD but also a close correlation between highly expressed SNAI2 and these three immune cell subsets in CAD patients.ConclusionIn conclusion, these biomarkers have important significance in the diagnosis of CAD patients. Eight EMT-related lncRNAs and SNAI2 can improve our understanding of the molecular mechanism between EMT and CAD.

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Vitamin D Receptor (VDR) Gene Polymorphisms and Risk of Coronary Artery Disease (CAD): Systematic Review and Meta-analysis

Cited by 18 publications

References 45 publications

Four common vitamin D receptor polymorphisms and coronary artery disease susceptibility: A trial sequential analysis

Four common vitamin D receptor polymorphisms and coronary artery disease susceptibility: A trial sequential analysis

Vitamin D-Related Single Nucleotide Polymorphisms as Risk Biomarker of Cardiovascular Disease

Epithelial-Mesenchymal Transition-Related lncRNAs And SNAI2 Are Potential Biomarkers in Coronary Artery Disease

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