Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome

Introduction: Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances including insulin resistance (IR), which might be related to vitamin D metabolism. We aimed to investigate the association of polymorphisms in the vitamin D receptor (VDR) gene as well as vitamin D level-associated genes with metabolic and endocrine parameters in PCOS women. Moreover, we examined whether there are associations with PCOS susceptibility. Methods: Metabolic, endocrine, and anthropometric measurements and oral glucose tolerance tests were performed in 545 PCOS and 145 control women. Genotyping of VDR (Cdx2, Bsm-I, Fok-I, Apa-I, and Taq-I), GC, DHCR7, and CYP2R1 polymorphisms was performed. Results: 25-Hydroxyvitamin D (25(OH) D) levels showed significant negative correlation with IR and positive correlation with insulin sensitivity (P < 0.05 for all) in PCOS women. In PCOS women, the VDR Cdx2 'AA' genotype was associated with lower fasting insulin (P=0.039) and homeostatic model assessment-IR (P=0.041) and higher quantitative insulin-sensitivity check index (P=0.012) and MATSUDA index (P=0.003). The VDR Apa-I 'AA' genotype was associated with lower testosterone (P=0.028) levels. In PCOS women, 170 women (31.2%) presented with 25(OH) D levels < 20 ng/ml. PCOS women carrying the GC 'GG' genotype and the DHCR7 'GG' genotype had a significantly higher risk for 25(OH) D levels <20 ng/ml (OR 2.53 (1.27-5.06), P=0.009, and OR 2.66 (1.08-6.55), P=0.033 respectively) compared with PCOS women carrying the GC 'TT' genotype and DHCR 'TT' genotype in multivariate analyses. We observed no association of genetic variations and PCOS susceptibility. Conclusion: VDR and vitamin D level-related variants are associated with metabolic and endocrine parameters including 25(OH)D levels in PCOS women.