Genetic variant in vitamin D-binding protein is associated with metabolic syndrome and lower 25-hydroxyvitamin D levels in polycystic ovary syndrome: A cross-sectional study

Santos, Betânia Rodrigues dos; Lecke, Sheila Bünecker; Spritzer, Poli Mara

doi:10.1371/journal.pone.0173695

Cited by 25 publications

(29 citation statements)

References 57 publications

(59 reference statements)

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“…In contrast to these positive findings, the lack of association seen between polymorphisms in VDR in our study contrasts with findings of a recent meta-analysis reporting that the VDR ApaI (rs7975232) polymorphism associated with susceptibility to PCOS in Asian populations (aOR for allelic model, C vs A, 1.19; 95% CI 1.07 to 1.34) 6 . The lack of association seen for SNPs in DBP is consistent with findings of both the other studies that have investigated polymorphisms in this gene 26,27 .…”

Section: Discussionsupporting

confidence: 90%

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

Lone

Riaz

Eusaph³

et al. 2020

Sci Rep

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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 ...

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Section: Discussionsupporting

confidence: 90%

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

Lone

Riaz

Eusaph³

et al. 2020

Sci Rep

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“…In a meta‐analysis of 14 observational studies, serum 25(OH)D levels were significantly lower among women with PCOS ( n = 1,150) compared with healthy controls ( n = 1,162) . Low vitamin D levels have also been associated with an aggravation of metabolic features in women with PCOS, including higher BMI and testosterone levels , as well as higher incidence of metabolic syndrome . A cross‐sectional study by our group in 76 women ( n = 42 with PCOS) found that 25(OH)D levels were lower in women with PCOS and a BMI > 25 kg m −2 and were associated with reduced insulin sensitivity (measured by hyperinsulinaemic clamp) in these women compared with controls .…”

Section: Vitamin D and Polycystic Ovary Syndromementioning

confidence: 85%

Vitamin D and cardiometabolic disorders: a review of current evidence, genetic determinants and pathomechanisms

2018

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Vitamin D deficiency has been implicated in the pathophysiology of cardiometabolic disorders including obesity, type 2 diabetes mellitus, cardiovascular diseases and polycystic ovary syndrome. Despite a large number of experimental and observational studies supporting a role for vitamin D in these pathologies, randomized controlled trials have reported little to no effect of vitamin D supplementation in the prevention or treatment of these disorders, although some results remain ambiguous. Polymorphisms in genes related to vitamin D metabolism, particularly in the vitamin D receptor and binding protein and the metabolizing enzyme 1-α-hydroxylase, have emerged as potential contributors to these divergent results. It is now becoming increasingly recognized that the effects and potential benefits of vitamin D supplementation may vary by several factors including vitamin D deficiency status, ethnicity and/or the presence of genetic variants, which affect individual responses to supplementation. However, these factors have seldom been explored in the available literature. Future trials should consider inter-individual differences and, in particular, should aim to clarify whether certain subgroups of individuals may benefit from vitamin D supplementation in the context of cardiometabolic health.

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“…The clinical, hormonal and metabolic characteristics of the studied population have been previously described [ 24 ]. Women with PCOS were younger than controls (22.9 ± 6.7 vs. 25.2 ± 7.7 years, p = 0.013), and presented higher BMI (29.7 ± 6.4 vs. 27.0 ± 6.1 kg/m 2 , p = 0.001) and higher frequency of overweight/obesity ( p = 0.002) and of MetS ( p < 0.001).…”

Section: Resultsmentioning

confidence: 99%

“…This is a cross-sectional study including 191 patients with PCOS and 100 non-hirsute women with regular, ovulatory cycles, recruited by advertisement in the local media. The characteristics of the study sample have been described elsewhere [ 24 ]. PCOS was diagnosed according to Rotterdam criteria [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

Apa-I polymorphism in VDR gene is related to metabolic syndrome in polycystic ovary syndrome: a cross-sectional study

Santos

Lecke

Spritzer

2018

Reprod Biol Endocrinol

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BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine disorder determined by polygenic traits as well as environmental factors. Lower vitamin D levels have been detected in PCOS women and related to hormone and metabolic disturbances. Vitamin D acts in tissues through the vitamin D receptor (VDR). VDR gene variants have been associated with worse metabolic profile in the general population. We investigated the genotype and haplotype distribution of the Bsm-I (rs1544410), Apa-I (rs7975232), and Taq-I (rs731236) VDR gene polymorphisms in PCOS and non-hirsute women from southern Brazil. We further investigated the associations of these gene variants and their haplotypes with PCOS, vitamin D levels, and metabolic abnormalities, including the metabolic syndrome (MetS).MethodsA group of 191 women with PCOS (Rotterdam criteria) and 100 non-hirsute controls with regular ovulatory cycles were genotyped for all polymorphisms by real-time PCR, with allelic discrimination assays. MetS and the cutoffs for its isolated components were defined in accordance with the Joint Scientific Statement.ResultsWomen with PCOS were younger and had significantly higher BMI and total testosterone levels than controls (p < 0.05). The frequency of MetS in PCOS and controls was 26.5% and 4.8% respectively. The CC genotype of Apa-I entailed higher risk of MetS in PCOS (OR: 2.133; 95% CI 1.020–4.464, p = 0.042), and was associated with higher systolic blood pressure (p = 0.009), total cholesterol (p = 0.040), and LDL-cholesterol (p = 0.038) in both PCOS and control groups (two-way ANOVA). The frequencies of VDR haplotypes were similar in PCOS and control women.ConclusionsThe present results suggest that the Apa-I variant in VDR gene may be associated with MetS in southern Brazilian women with PCOS, and with blood pressure, total cholesterol, and LDL-c in women with and without PCOS.

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Genetic variant in vitamin D-binding protein is associated with metabolic syndrome and lower 25-hydroxyvitamin D levels in polycystic ovary syndrome: A cross-sectional study

Cited by 25 publications

References 57 publications

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

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

Vitamin D and cardiometabolic disorders: a review of current evidence, genetic determinants and pathomechanisms

Apa-I polymorphism in VDR gene is related to metabolic syndrome in polycystic ovary syndrome: a cross-sectional study

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