Department of Biochemistry, Room No. 302, Third Floor, Casualty Building, Vardhman Mahavir Medical College and Safdarjang Hospital, New Delhi, India.
Department of Biochemistry, S.M.B.T. Institute of Medical Science and Research Centre, Nashik, Maharashtra, India.
Eur J Nutr. 2018 Mar;57(2):703-711. doi: 10.1007/s00394-016-1357-z. Epub 2016 Dec 23.
Polycystic ovarian syndrome (PCOS) is the most common endocrine abnormality among women of reproductive age and is usually associated with oligo-ovulation/anovulation, obesity, and insulin resistance. Hypovitaminosis D may also be a primary factor in the initiation and development of PCOS. However, little is known about the role of genetic variation in vitamin D metabolism in PCOS aetiology. Therefore, we studied the genetic polymorphisms of CYP2R1 and vitamin D binding protein (VDBP) in an Indian population.
Serum vitamin D was measured by ELISA. Genotyping of VDBP single nucleotide polymorphisms (SNPs) rs7041 (HaeIII; G>T) and rs4588 (StyI; A>C) and CYP2R1 SNP rs2060793 (HinfI; A>G) was carried out by restriction fragment length polymorphism in 50 cases of PCOS that were compared with 50 age-matched healthy women.
Vitamin D levels were found to be significantly lower in women with PCOS (p = 0.008) than in age-matched controls. There was no significant difference in genotype frequencies of all three polymorphisms (rs7041, rs4588, and rs2060793) between PCOS and control women. In women with a vitamin D deficiency (<20 ng/ml), the GT allele of the VDBP SNP rs7041 (p value =0.04), the VDBP allelic combination Gc1F/1F (T allele of rs4588 and C allele of rs7041) (p value =0.03), and the GA allele of the CYP2R1 SNP rs2060793 (p = 0.05) were associated with an increased risk of developing PCOS.
The present study shows that the GT allele of VDBP SNP rs7041, the VDBP allelic combination (GC1F/1F), and GA allele of CYP2R1 SNP rs2060793 in vitamin D deficient women increase the risk of PCOS.
多囊卵巢综合征（PCOS）是育龄妇女最常见的内分泌异常，通常与少卵/无排卵、肥胖和胰岛素抵抗有关。维生素 D 缺乏也可能是 PCOS 发病的主要因素。然而，关于维生素 D 代谢的遗传变异在 PCOS 发病机制中的作用知之甚少。因此，我们在印度人群中研究了 CYP2R1 和维生素 D 结合蛋白（VDBP）的遗传多态性。
通过 ELISA 法测定血清维生素 D 水平。采用限制性片段长度多态性方法对 50 例 PCOS 患者和 50 例年龄匹配的健康女性的 VDBP 单核苷酸多态性（SNP）rs7041（HaeIII；G>T）和 rs4588（StyI；A>C）及 CYP2R1 SNP rs2060793（HinfI；A>G）进行基因分型。
发现 PCOS 患者的维生素 D 水平明显低于年龄匹配的对照组（p=0.008）。三种多态性（rs7041、rs4588 和 rs2060793）的基因型频率在 PCOS 患者与对照组之间无显著差异。在维生素 D 缺乏症（<20ng/ml）的女性中，VDBP SNP rs7041 的 GT 等位基因（p 值=0.04）、VDBP 等位基因组合 Gc1F/1F（rs4588 的 T 等位基因和 rs7041 的 C 等位基因）（p 值=0.03）和 CYP2R1 SNP rs2060793 的 GA 等位基因（p=0.05）与 PCOS 发病风险增加相关。
本研究表明，维生素 D 缺乏的女性中 VDBP SNP rs7041 的 GT 等位基因、VDBP 等位基因组合（GC1F/1F）和 CYP2R1 SNP rs2060793 的 GA 等位基因增加了 PCOS 的发病风险。
