Vitamin D Deficiency and VDR Gene Variants in Polycystic Ovary Syndrome: A Case-Control Study

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder in reproductive-aged women and adolescents. Vitamin D deficiency (VDD) and genetic variations in the vitamin D receptor (VDR) pronouncedly influence its manifestations. The interplay between VDD and VDR polymorphisms has an umbrella effect on the endocrine and metabolic milieu of PCOS, underscoring the importance of vitamin D (VD) in its management. This study tried to find out the association between VDD and single-nucleotide polymorphisms (SNPs) in the VDR gene in the differential pathophysiological manifestations of PCOS in the ethnic population of West Bengal, India. The case-control study was conducted involving 170 PCOS women (ages 17-36 years) and 150 of their gender, and age and ethnicity-matched healthy controls. VDD was assessed along with the association of VDR polymorphisms [BsmI (rs1544410) and FokI (rs2228570)] with the nutritional and biochemical indices. Bioelectrical impedance (anthropometric indices), structured questionnaires (sociodemographic characteristics, solar-UVB exposure and nutritional status), haematological estimation (VD and other necessary parameters) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP, VDR-SNPs) were employed in this study. In the PCOS population, the BsmI-VDR-based VD cutoff level was 19.17 ng/ml [asymptotic sig.: 0.000, with area under the curve (AUC): 0.894, sensitivity: 0.950, and specificity: 0.657] and the FokI-VDR-based VD cutoff level was 17.67 ng/ml [asymptotic sig.: 0.000, with AUC: 0.947, sensitivity: 0.875, and specificity: 0.732] derived by receiver operating characteristic (ROC) curve analysis. VDR-SNPs were further stratified by performing Sanger sequencing. Significant correlations were found between VDR variants and hyperandrogenism (HA), insulin resistance (IR), inflammatory markers, and obesity indices of PCOS patients. Mutant (BsmI-bb/Bb and FokI-ff/Ff) VDR genotypes were found to be influential upon the metabolic and cutaneous features of PCOS patients, suggesting a genetic basis for VD-related disturbances in PCOS. This study accentuates the need for personalised therapeutic strategies, particularly VD supplementation, based on genetic profiles to manage the severity and prevalence of PCOS and its associated metabolic deregulations.