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

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.

METHODS

In this study, T2DM cases ( = 100) and controls ( = 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 ( > 0.05). The T2DM was shown to be strongly correlated with hypermethylation (-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 ( < 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 ( < 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.