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

• Published in: Journal of diabetes and metabolic disorders Vol. 22; no. 2; pp. 1443 - 1451
• Main Authors: Tarfeen, Najeebul, Masoodi, Shariq Rashid, Nisa, Khair Ul, Ali, Shafat, Ahmad, Mir Bilal, Ganai, Bashir Ahmad
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 29.07.2023; BioMed Central Ltd
• Subjects: Alfacalcidol; Calcifediol; Diabetes; Diabetics; Endocrinology; Gene expression; Genes; Leptin; Medicine; Medicine & Public Health; Metabolic Diseases; Methylation; Research Article; Tumor necrosis factor; Type 2 diabetes; Vitamin D; Illinois; Inflammatory biomarkers; Promoter methylation; Vitamin D; VDR; Diabetes mellitus
• ISSN: 2251-6581; 2251-6581
• DOI: 10.1007/s40200-023-01266-6

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 ( 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.