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Down regulation of VDR gene expression in metabolic syndrome and atherosclerosis’ patients: Cause or consequence?
Gene ( IF 2.6 ) Pub Date : 2020-12-15 , DOI: 10.1016/j.gene.2020.145341
Maria Eduarda de Albuquerque Borborema , Dinaldo C. Oliveira , Jaqueline de Azevêdo Silva

Background

Metabolic syndrome (MS) features a set of clinical manifestations with an increased risk of atherosclerosis development. Vitamin D3 (VD3) pathway influences upon clinical features in MS as well in the formation of atherosclerotic plaque. VD3 acts through the vitamin D receptor (VDR), regulating the transcription of several genes involved in the immune response, growth and homeostasis.

Aim

To evaluate whether VDR mRNA levels vary in MS patients according clinical features and atherosclerosis severity.

Methods

We included eighty individuals distributed into four groups: 1 group with MS (n = 20), 2 groups with atherosclerosis based on the report from the angiography (severe lesions - SL and primary lesions - PL) and 1 group enclosing healthy individuals (HC). The expression assays of VDR gene was performed using Real Time qPCR, with specific Taqman probes. We applied the Shapiro-Wilk, Chi-Squared and Student’s T-tests for statistical analyses considering as statistically significant p < 0.05.

Results

Patients with MS as well with coronary stenosis present a down-regulation of VDR gene expression (-9.01 FC, p = 2.497 × 10-13; −13.62 FC, p = 7.489 × 10-13, respectively) when compared to control group. We also evaluated the VDR gene expression according to atherosclerosis severity, SL and PL patients present a downregulation of −31.51 FC and −8.48 FC, respectively, when compared with healthy controls group (p = 1.369 × 10-11; p = 1.647 × 10-11). When compared different degrees of atherosclerosis severity (SL versus PL) SL present a downregulation of −3.71 FC, when compared to PL group (p = 0.006).

Conclusion

VDR is downregulated in patients with MS and according atherosclerosis severity. The differential expression of this gene is related to this hormone functions being an ex-vivo gene target for assessment in MS and atherosclerosis.



中文翻译:

下调代谢综合征和动脉粥样硬化患者的VDR基因表达:原因还是后果?

背景

代谢综合征(MS)具有一系列临床表现,增加了患动脉粥样硬化的风险。维生素D 3(VD 3)途径影响MS的临床特征以及动脉粥样硬化斑块的形成。VD 3通过维生素D受体(VDR)起作用,调节涉及免疫应答,生长和体内平衡的几种基因的转录。

目标

评估MS患者的VDR mRNA水平是否根据临床特征和动脉粥样硬化严重程度而变化。

方法

根据血管造影的报告(严重病变-SL和原发性病变-PL),我们将80位患者分为四组:1组MS(n = 20),2组动脉粥样硬化(重度病变-SL和原发性病变-PL)和1个封闭健康个体(HC) 。VDR基因的表达测定是使用实时qPCR和特异性Taqman探针进行的。我们将Shapiro-Wilk,Chi-Squared和Student's T检验用于统计分析,考虑到统计学上的显着性p  <0.05。

结果

与对照组相比,MS患者和冠状动脉狭窄患者的VDR基因表达也下调(分别为-9.01 FC,p  = 2.497 ×10 -13; -13.62 FC,p  = 7.489×10 -13)。我们还根据动脉粥样硬化的严重程度评估了VDR基因的表达,与健康对照组相比,SL和PL患者分别呈现−31.51 FC和−8.48 FC的下调(p  = 1.369×10 -11p  = 1.647×10 -11)。比较不同程度的动脉粥样硬化严重程度(SL与PL组相比,PL)SL的表达下调为-3.71 FC(p  = 0.006)。

结论

MS患者并根据动脉粥样硬化严重程度下调VDR。该基因的差异表达与该激素功能有关,该激素功能是用于MS和动脉粥样硬化评估的离体基因靶标。

更新日期:2020-12-23
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