Quantitative methylation level of the EPHX1 promoter in peripheral blood DNA is associated with polycystic ovary syndrome.
Quantitative methylation level of the EPHX1 promoter in peripheral blood DNA is associated with polycystic ovary syndrome.
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外周血 DNA 中 EPHX1 启动子的定量甲基化水平与多囊卵巢综合征相关
DOI：
10.1371/journal.pone.0088013
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Sang Q;Li X;Wang H;Wang H;Zhang S;Feng R;Xu Y;Li Q;Zhao X;Xing Q;Jin L;He L;Wang L
类固醇合成和代谢途径在多囊卵巢综合征的病理生理中发挥重要作用，但迄今为止还没有关于类固醇合成途径中与多囊卵巢综合征相关的特定基因甲基化谱的研究。在这里，我们使用MassARRAY定量甲基化分析来确定64个外周血样本中EPHX1、SRD5A1和CYP11A1启动子中每个CpG位点或簇的甲基化水平。我们在一个由116人组成的独立队列中进一步检测了EPHX1的甲基化水平。最后，我们研究了EPHX1在KGN细胞系类固醇生成中的作用。对于SRD5A1和CYP11A1，患者与对照组之间的甲基化水平无显著差异。然而，对于EPHX1，几个连续的CpG位点和簇的甲基化水平被发现与PCOS显著相关。在第一个由64人组成的队列中，一些CpG簇或位点的甲基化水平在患者中显著低于对照组，如簇13-14 （P<0.05）、15-16 （P<0.001）和19-24 （P<0.001）以及位点CpG_53 （P<0.01）和CpG_54 （P<0.05）。在分化的甲基化位点和聚类中，PCOS患者CpG聚类13-14和CpG聚类19-24的甲基化水平在第二队列116人中显著低于对照组（P<0.05）。此外，在KGN细胞中的敲低和过表达实验表明，EPHX1可以调节雌二醇浓度，这表明EPHX1在类固醇生成中起作用。我们的研究表明EPHX1启动子的甲基化可能与PCOS有关。该研究提供了甲基化在PCOS中发挥重要作用的直接证据，并证明了EPHX1在女性生殖中的新作用。
Steroid synthesis and metabolic pathways play important roles in the pathophysiology of PCOS, but until now there have been no studies on the methylation profiles of specific genes in steroid synthesis pathways that are known to be associated with PCOS. Here we used MassARRAY quantitative methylation analysis to determine the methylation levels of each CpG site or cluster in the promoters of EPHX1, SRD5A1, and CYP11A1 in 64 peripheral blood samples. We further examined the methylation level of EPHX1 in an independent cohort consisting of 116 people. Finally, we investigated the role of EPHX1 in steroidogenesis in the KGN cell line. For SRD5A1 and CYP11A1, there was no significant difference in methylation level between patients and controls. For EPHX1, however, the methylation levels of a few consecutive CpG sites and clusters were found to be significantly associated with PCOS. The methylation levels of a number of CpG clusters or sites were significantly lower in patients than in controls in the first cohort consisting of 64 people, such as clusters 13–14 (P<0.05), 15–16 (P<0.001), and 19–24 (P<0.001) and sites CpG_53 (P<0.01) and CpG_54 (P<0.05). Among differentiated methylation sites and clusters, the methylation levels of the CpG cluster 13–14 and CpG cluster 19–24 in PCOS patients were significantly lower than in controls in the second cohort of 116 people (P<0.05 for both). In addition, knockdown and overexpression experiments in KGN cells showed that EPHX1 can regulate estradiol concentrations, and this indicates a role for EPHX1 in steroidogenesis. Our study has demonstrated that methylation of the EPHX1 promoter might be associated with PCOS. This study provides direct evidence that methylation plays an important role in PCOS and demonstrates a novel role for EPHX1 in female reproduction.
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影响因子：
4.8
作者：
Hattori, N;Fujiwara, H;Ueda, M
通讯作者：
Ueda, M
影响因子：
3.5
作者：
Gharani, N;Waterworth, DM;Williamson, R
通讯作者：
Williamson, R
影响因子：
5.8
作者：
Goodarzi, Mark O.;Shah, Nissar A.;Azziz, Ricardo
通讯作者：
Azziz, Ricardo
DOI：
10.1159/000015164
发表时间：
1998-01-01
期刊：
CYTOGENETICS AND CELL GENETICS
影响因子：
--
作者：
Hartsfield, JK;Sutcliffe, MJ;Saari, JA
通讯作者：
Saari, JA
影响因子：
3.2
作者：
Popp, Simone L.;Abele, Ina S.;Knabbe, Cornelius
通讯作者：
Knabbe, Cornelius