Genotype-independent association between vitamin D deficiency and polycystic ovarian syndrome in Lahore, Pakistan

Abstract

Both vitamin D deficiency and single nucleotide polymorphisms (SNPs) in the gene encoding the vitamin D receptor (VDR) have been widely reported to associate with susceptibility to polycystic ovarian syndrome (PCOS). A case-control study was conducted to study the influence of vitamin D status and genotpye for 24 SNPs in four genes in the vitamin D pathway (VDR, DBP, CYP27B1, CYP24A1) on PCOS. Statistical analyses were conducted to identify phenotypic and genotypic factors associated with risk of pcoS and to test for interactions between genotype and vitamin D status. pcoS was independently associated with lower age, higher body mass index, lower waist-hip ratio, vitamin D deficiency (serum 25-hydroxyvitamin D concentration <10 ng/mL), lack of outdoor exercise, increased fasting glucose and a family history of PCOS in at least one first degree relative. No statistically significant association was observed between the genotype of any SNP investigated and risk of PCOS, either as a main effect or in interaction with vitamin D status. We report a strong and independent association between vitamin D deficiency and risk of PCOS in Pakistan, that was not modified by genetic variation in the vitamin D pathway.Polycystic ovary syndrome (PCOS) is the most common reproductive, endocrine and metabolic disorder in women of reproductive age 1 . Globally, the prevalence of PCOS ranges from 4 to 21%, as defined using NIH 1990 and Rotterdam 2003 criteria 2 . Epidemiological data from Pakistan are scarce, but the prevalence of PCOS has been reported to be particularly high among women of South Asian ethnic origin 3,4 .PCOS is thought to arise as a result of the interplay between genetic and environmental factors 5 . A growing body of literature indicates that vitamin D deficiency may be a risk factor: meta-analyses of observational studies reveal independent associations between PCOS and low serum concentrations of 25-hydroxyvitamin D (25[OH] D, the major circulating vitamin D metabolite) as well as single nucleotide polymorphisms [SNPs] in the gene encoding the vitamin D receptor (VDR) 6-11 . However, data relating to vitamin D status among women with PCOS in Pakistan are lacking. Moreover, studies in the field have not yet tested for main effects of SNPs in the genes encoding the 1-alpha hydroxylase enzyme CYP27B1 (which converts 25[OH]D to its active metabolite 1,25-dihydroxy vitamin D) or the vitamin D 24-hydroxylase enzyme CYP24A1 (which converts 25[OH]D to its major inactive catabolite 24R,25-dihydroxy vitamin D). Neither have they tested for interactions between SNPs in the vitamin D pathway and vitamin D status in influencing the risk of PCOS.We have previously demonstrated that genetic variation in the vitamin D pathway can modify the influence of vitamin D deficiency and supplementation on clinical phenotype in the context of tuberculosis 12-14 . We, therefore, conducted a case control study in Lahore, Pakistan, to determine whether vitamin D deficiency and SNPs in four vitamin D pathway genes might influence the risk ...

Polycystic Ovarian Syndrome (PCOS) and its association with VDR gene variants Cdx2 (rs11568820) and ApaI (rs7975232): Systematic Review, Meta-analysis and In silico analysis

“…VDR plays an important role in the pathogenesis of PCOS by mediating the action of Vitamin D and also affecting the insulin signaling pathways (Pittas et al, 2007). Another study investigatedthat lower vitamin D was independently associated with risk of PCOS but the genetic variationof VDR had no effect (Lone et al, 2020), whereas a recent study in a model organism has investigated the role of Vitamin D3 in the ovary in PCOS indicating reduced levels of Vitamin D3 concentration and implication in the PCOS pathogenesis (Grzesiak et al, 2021). The ndings of the VDR gene as a candidate gene that plays a role or affects PCOS pathogenesis have been contradictory.…”

The relationship between Vitamin D deficiency and polycystic ovary syndrome

“…Previous studies have shown a connection between PCOS and vitamin D deficiency. There is adequate evidence in the literature to suggest that vitamin D deficiency exacerbates the risk of PCOS 31 , 33 . The fact that the connection between the two cannot be explained may be due to the complex etiology of PCOS.…”