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

Abstract

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 (PZ0.039) and homeostatic model assessment-IR (PZ0.041) and higher quantitative insulin-sensitivity check index (PZ0.012) and MATSUDA index (PZ0.003). The VDR Apa-I ' AA' genotype was associated with lower testosterone (PZ0.028) 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), PZ0.009, and OR 2.66 (1.08-6.55), PZ0.033 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.

Influence of a positive family history of both type 2 diabetes and PCOS on metabolic and endocrine parameters in a large cohort of PCOS women

“…We found an about 1.7-fold increased risk of prediabetes and insulin resistance and twofold increased risk of MS and dyslipidaemia in PCOS women with a positive FHx of T2DM. Thus, our findings are consistent with a genetic basis for metabolic disturbances in PCOS, which has been suggested previously (15,25,26). Interestingly, PCOS women with a positive T2DM FHx were more likely to have a positive PCOS FHx suggesting a common genetic background of both diseases.…”

MECHANISMS IN ENDOCRINOLOGY: Thyroid and polycystic ovary syndrome

“…Moreover, polymorphisms of the CYP27B1 hydroxylase gene catalyzing the conversion of 25 hydroxyvitamin D 3 (25(OH)D) to its active form were also associated with HT (69). Vitamin D levels were associated with VDR and vitamin D level-related genetic variants (70,71). The latter finding was confirmed by Lin et al (72).…”

“…Associations between the low 25(OH)D levels and features of metabolic syndrome (77), and between VDR and vitamin D-related polymorphisms and metabolic and endocrine parameters, but not with PCOS susceptibility per se, have been shown (70). However, in PCOS women from Iran, an association of VDR ApaI polymorphisms with PCOS susceptibility was found (40).…”

Vitamin D and assisted reproduction: should vitamin D be routinely screened and repleted prior to ART? A systematic review

“…While some studies reported lower levels of vitamin D in women with PCOS [46,47], other studies suggested that levels are comparable [48] or even higher compared to women with PCOS [49]. Several studies have reported an inverse relationship between body mass index (BMI) and vitamin D levels in PCOS patients [50][51][52].…”

“…Wehr et al [46] identified polymorphisms in the VDR gene associated with vitamin D levels in PCOS women, suggesting a role of vitamin D in the pathogenesis of PCOS. In a recent systematic review of 275 publications reporting on the effects of advanced glycation end products (AGEs) on female reproduction, Merhi [54] concluded that AGEs might contribute to the etiology of PCOS and infertility.…”