Hypermethylation and Down Regulation of Vitamin D Receptor (VDR) as contributing factors for Polycystic Ovary Syndrome (PCOS)- A Case Control study from Kashmir, North India.

Abstract

Abstract Background: Polycystic Ovarian Syndrome (PCOS) is a prevalent endocrinopathy disorder affecting a significant population of women of reproductive age globally. A myriad set of complexly intertwined factors ranging from etiological, genetic, and epigenetic causes affect this disorder. Out of the different factors, Vitamin D shows an imperative aspect in the health and fertility of women with polycystic ovary syndrome (PCOS). The importance of vitamin D is facilitated by vitamin D receptor (VDR), a ligand-dependent transcription factor in the steroid/ thyroid hormone receptor superfamily that controls the pleiotropic biological properties of vitamin D. Purpose: The purpose of this study was to evaluate the role of promoter methylation of the vitamin D receptor (VDR) gene, a transcription factor with numerous biological utilities, with its relative expression and clinico-pathological findings and outcomes. Methodology: A total of 200 blood samples were collected, 100 from PCOS case subjects and 100 from the normal healthy controls respectively, which were assessed by RT-PCR for determining the expression summary. MS- PCR for analyzing the promoter methylation status of the VDR gene. Blood samples were withdrawn respectively for each case and the control study separately experimented for different stages for the given study, of which estimation of vitamin D was also a part. Results: In this study, the occurrence of methylation status in PCOS females was found 84% compared to normal controls where it was 62%, with a p-value< 0.0001. The results of the hyper-methylated VDR gene revealed a significant inverse correlation over the expression analysis (0.55 times downregulated). Moreover, compared to the Vitamin D parameter, the hypermethylation and expression analysis of the VDR promoter was found to correspond to some associations with PCOS. Certain case and control study analyses showed that patients with normal Vitamin D levels showed less indicative effects of PCOS and vice-versa. Conclusion: Our study, being exclusive from Kashmir, one of the foremost specified that Vitamin D Receptor (VDR) confirms anomalous methylation configuration in PCOS with subsequent downregulation in the expression. Hypermethylation of the VDR gene is associated with the downregulation of its gene expression.