Down regulation of VDR gene expression in metabolic syndrome and atherosclerosis' patients: Cause or consequence?

Abstract

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