Abstract
Vitamin D deficiency has been related to metabolic syndrome (MetS) in polycystic ovary syndrome (PCOS). The vitamin D-binding protein (DBP) is the main protein involved in vitamin D transport. Two single-nucleotide polymorphisms (SNPs) of the DBP gene, rs4588 and rs7041, have been associated with low circulating levels of 25-hydroxyvitamin D [25(OH)D] in various populations, but not in women with PCOS. Therefore, we determined the genotype and haplotype distribution of DBP gene polymorphisms and investigated the associations between these genetic variants and their haplotypes with PCOS, MetS, and 25(OH)D levels in women with PCOS and controls from the South of Brazil. The sample included 291 women (191 with PCOS and 100 controls). All participants were genotyped for polymorphisms rs2282679, rs4588, and rs7041. Serum 25(OH)D levels were determined in a subset of 102 participants. Women with PCOS were younger and had significantly higher body mass index, blood pressure, and insulin resistance than the control group (p<0.05). The prevalence of MetS in PCOS and controls was 26.5% and 4.8% respectively. Levels of 25(OH)D were lower in PCOS women with MetS, even after adjustment for age (p = 0.033). No associations were observed between PCOS and the polymorphisms or their haplotypes. A higher frequency of genotype TT of rs7041 was found in PCOS participants with MetS (OR: 2.21, 95%CI:1.08–4.52; p = 0.027). This same genotype was associated with lower 25(OH)D levels in both PCOS and control women (OR: 4.40, 95%CI:1.62–12.00; p = 0.002). In conclusion, these findings indicate that DBP gene polymorphisms and their haplotypes are not directly associated with PCOS. In contrast, the TT genotype of SNP rs7041 was associated with MetS in PCOS women, and with lower 25(OH)D levels in both PCOS and control groups.
Highlights
Polycystic ovary syndrome (PCOS), a heterogeneous disease characterized by chronic anovulation and manifestations of hyperandrogenism [1, 2], affects between 9% and 18% of women of reproductive age, depending on diagnostic criteria [1,2,3]
vitamin D receptor (VDR) is expressed in many tissues and organs, such as those involved in calcium homeostasis, glucose metabolism, and reproduction [14], whereas D-binding protein (DBP) is the main protein involved in vitamin D transport [15, 16]
Data are expressed as mean ± standard deviation (SD). p value by Student’s t test, adjusted for age. 25(OH)D: 25-hydroxyvitamin D. doi:10.1371/journal.pone.0173695.g001
Summary
Polycystic ovary syndrome (PCOS), a heterogeneous disease characterized by chronic anovulation and manifestations of hyperandrogenism [1, 2], affects between 9% and 18% of women of reproductive age, depending on diagnostic criteria [1,2,3]. Vitamin D deficiency may be linked to central obesity, lipid profile, and body mass index (BMI) in these women [7,8,9,10,11,12,13]. Both the vitamin D receptor (VDR) and the vitamin D-binding protein (DBP) play a key role in vitamin D metabolism. VDR is expressed in many tissues and organs, such as those involved in calcium homeostasis, glucose metabolism, and reproduction [14], whereas DBP is the main protein involved in vitamin D transport [15, 16]. Two well-studied single-nucleotide polymorphisms (SNPs) of the DBP gene, rs4588 and rs7041, have been previously shown to be strongly associated with low circulating 25-hydroxyvitamin D [25(OH)D] levels in genomewide association studies [17, 18] and in various populations [19,20,21,22,23,24]
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