Polymorphisms of Vitamin D Receptor and the Effect on Metabolic and Endocrine Abnormalities in Polycystic Ovary Syndrome: A Review

Abstract

Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorder in women of reproductive age. Vitamin D and its receptor are thought to play an important role in PCOS susceptibility, although the impact of vitamin D receptor (VDR) polymorphisms on the hormonal and metabolic profile is still controversial. A literature search in PubMed and Embase was performed up to September 2020 for case-control studies in women suffering from PCOS, with outcome related to VDR polymorphisms effect on metabolic/endocrine disturbances. We have found 16 eligible studies including 2566 women with PCOS and 2430 controls. ApaI polymorphism seemed to be associated with hyperandrogenism in both Asian and Caucasian population. FokI variant was correlated with metabolic/endocrine parameters especially in Asian population, while a relation between Cdx2 genotypes and insulin sensitivity was observed in both ethnicities. VDR polymorphisms have an important role in PCOS development and related hormonal and metabolic abnormalities. Few case-control studies analysed the interaction between VDR variants and metabolic/endocrine parameters with the majority of the articles focused on the Asian region. Further research on various ethnic populations with larger sample size are still needed for a definitive conclusion, in order to allow early diagnosis and prevention of PCOS comorbidities.

Vitamin D and infertility

“…There is a vitamin D response element in the promoter region of the insulin gene, and vitamin D receptor polymorphisms have been studied as a proposed cause for the relationship between vitamin D serum levels, insulin resistance and hyperandrogenism [38]. A recent review article concluded that the ApaI polymorphism specifically was associated with hyperandrogenism in Asian and white populations, while the FokI polymorphism was associated with metabolic and endocrine disturbances primarily in the Asian population [39].…”

PCOS Physiopathology and Vitamin D Deficiency: Biological Insights and Perspectives for Treatment

“…All of this information, along with the reported key role of VDR in the regulation more than 3% of the human genome, prompted researchers to examine the real contribution of the VDR gene polymorphisms in metabolic and endocrine disturbance of PCOS [ 21 , 22 ]. Despite some evidence pointing to an influence of VDR gene variants in PCOS features, it is difficult to definitively establish a clear association of VDR polymorphisms with the development of PCOS [ 23 ].…”

Polycystic Ovarian Syndrome (PCOS) and its association with VDR gene variants Cdx2 (rs11568820) and ApaI (rs7975232): Systematic review, meta-analysis and in silico analysis

“…Polymorphisms in the Vitamin D receptor (VDR) have been linked to some of the clinical representations associated with PCOS (Reis et al, 2017). The gene is highly polymorphic, and its polymorphic markers namely FokI, BsmI, ApaI, TaqI, Tru9I, and Cdx2 have resulted in aslew of allelic variants that vary among ethnic groups (Vulcan et al, 2021). A previous meta-analysis with nine studies reported in 2019 has found the association of VDR ApaI (rs7975232) (C > A) gene polymorphism and PCOS outcome (Shi et al, 2019).…”