VDR downregulation and promoter hypermethylation as one of the causes for triggering type 2 diabetes mellitus: Clinical and molecular studies

VDR 下调和启动子高甲基化是引发 2 型糖尿病的原因之一:临床和分子研究

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作者:Najeebul Tarfeen, Shariq Rashid Masoodi, Khair Ul Nisa, Shafat Ali, Mir Bilal Ahmad, Bashir Ahmad Ganai

Background

Our present study was to investigate the methylation and Gene expression of the vitamin D receptor (VDR) gene in the causing T2DM and to determine the inflammatory biomarkers in exaggerating T2DM in Kashmiri population.

Conclusions

This study suggests the hypermethylation and down expression of VDR as one of the basis for causing T2DM in kashmiri individuals, exaggerated by enhanced degree of TNF-α, CRP, IL-6 and leptin and diminished concentration of IL-10 and adiponectin in T2DM.

Methods

In this study, T2DM cases (n = 100) and controls (n = 100) of Kashmiri population were designed. Blood samples were taken from both groups, and serum vitamin D levels, inflammatory biomarkers (TNF-α, IL-6, IL-10, CRP, Leptin and adiponectin) were estimated by ELISA. By using methylation-specific PCR (MS-PCR) and RT-PCR, respectively, the levels of methylation and expression were measured after the extraction of DNA and RNA.

Results

Studies using RT-PCR demonstrated that patients with diabetes had a lower degree of VDR expression than control subjects (P > 0.05). The T2DM was shown to be strongly correlated with hypermethylation (p-value < 0.001, OR 2.9; 95%CI 1.6-5.54). When compared to control groups, T2DM patients' levels of vitamin D in their serum were considerably lower (p < 0.01). Pro-inflammatory mediators like TNF-α, CRP, IL-6, and leptin levels were discovered to be higher, and concentrations of anti-inflammatory mediators like IL-10 and adiponectin were observed to be lower in people with T2DM than in people without the condition (p < 0.05). Conclusions: This study suggests the hypermethylation and down expression of VDR as one of the basis for causing T2DM in kashmiri individuals, exaggerated by enhanced degree of TNF-α, CRP, IL-6 and leptin and diminished concentration of IL-10 and adiponectin in T2DM.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40200-023-01266-6.

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