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

Abstract

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.

Association of the ESR1 (rs9340799), OLR1 (rs3736234), LIPC (rs2070895), VDR (rs2228570), and CETP (rs708272) Polymorphisms With Risk of Coronary Artery Disease in Iranian Patients

“…In addition, the TT genotype of rs2228570 exhibited an association with elevated levels of both LDL-c and HDL-c compared with the CC genotype. These results were consistent with previous studies that have also reported a notable correlation between the VDR (rs2228570) polymorphism and CAD risk in various populations, such as Chinese [46], Egyptian [47], and Iranian [48] populations. Moreover, a recent meta-analysis conducted by Tabaei et al [30] reinforced our results, demonstrating a significant association between the VDR (rs2228570) polymorphism and the risk of CAD.…”

The Role of Polymorphism in the Endothelial Homeostasis and Vitamin D Metabolism Genes in the Severity of Coronary Artery Disease

“…Moreover, this polymorphism may be predisposed to the development of premature CAD in healthy people with a family history of this disease over the next years [ 61 ]. According to the latest meta-analysis, the polymorphic variants rs2225870, rs1544410 and rs731236 are characterized by risk of CAD development, but the role of the rs7975232 polymorphism is ambiguous [ 62 , 63 ]. The role of genetic polymorphism in the VDR gene in CAD severity has been studied in only one article—the authors reported no associations between the rs1544410 and rs731236 polymorphisms with the severity of this disease [ 59 ].…”

Assessment of vitamin D levels in correlation with coronary CT angiography results in a Slovak Population

“…6,7 Importantly, the genetic polymorphism of the vitamin D receptor may alter its role, and variations in ethnicity, lifestyle, and geographic conditions could potentially influence its effects. 8 The objective of this study was to assess the correlation between vitamin D levels and the findings of coronary artery computed tomography (CT) angiography in a Slovakian population.…”