Genome‑wide DNA methylation analysis of uterosacral ligaments in women with pelvic organ prolapse.
Genome‑wide DNA methylation analysis of uterosacral ligaments in women with pelvic organ prolapse.
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DOI：
10.3892/mmr.2018.9656
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发表时间：
2019-01
影响因子：
3.4
通讯作者：
Lu D
中科院分区：
文献类型：
--
作者：
Zhang L;Zheng P;Duan A;Hao Y;Lu C;Lu D
骨盆器官脱垂(POP)是一个日益严重的健康问题，它损害了人们的生活质量，是由多种遗传和环境因素叠加引起的。由于子宫骶韧带(ULS)为盆腔器官提供了主要的支持，因此假设这些韧带的断裂(由于异常甲基化)可能会导致失去支持，并最终导致POP。本研究旨在探讨与对照组相比，POP患者ULS中是否存在甲基化异常。从5名患有POP的妇女和4名非POP的妇女的ULS中提取基因组DNA，作为对照，这些妇女因良性疾病而接受子宫切除术。使用Illumina Infinium甲基化EPICBeadChips Infinium人甲基化850K微珠阵列研究ULS中的总甲基化。与正常对照组相比，POP患者尿路上皮细胞中有3,723个CpG差异甲基化位点(Δβ<；0.14；P<；0.05)，其中高甲基化位点3,576个，低甲基化位点147个。在基因结构上，TSS1500和5‘端非翻译区高甲基化多于低甲基化。基因本体论分析表明，这些差异甲基化基因与“细胞形态发生”、“细胞外基质”、“细胞连接”、“蛋白质结合”和“鸟苷三磷酸酶活性”相关。发现了几条重要的途径，包括“局部黏附”和“细胞外基质-受体相互作用途径”。本研究提供的证据表明，患有和不患有POP的绝经妇女ULS的全基因组DNA甲基化存在差异，表观遗传学机制可能在一定程度上参与了POP的发病。
Pelvic organ prolapse (POP) is an increasingly serious health problem that impairs quality of life and is caused by multiple additive genetic and environmental factors. As the uterosacral ligaments (ULs) provide primary support for the pelvic organs, it was hypothesized that disruption of these ligaments (as a result of aberrant methylation) may lead to a loss of support and eventually contribute to POP. In the present study, whether there are any aberrant methylations in the ULs of patients with POP compared to those of controls was investigated. Genomic DNA was isolated from the ULs of five women with POP and four women without POP, as controls, undergoing hysterectomy for benign conditions. An Illumina Infinium Methylation EPICBeadChips Infinium Human Methylation 850 K bead array was used to investigate the total methylation in the ULs. There were 3,723 differentially methylated CpG sites (Δβ<0.14; P<0.05), including 3,576 hypermethylation and 147 hypomethylation sites in the ULs of patients with POP compared with the normal controls. There were more hypermethylated CpG sites, but a high ratio of hypomethylation between CpG islands and the N-shelf; in the gene structure, there was more hypermethylation than hypomethylation in TSS1500 and the 5′ untranslated region. Gene ontology analysis demonstrated that these differentially methylated genes were associated with ‘cell morphogenesis’, ‘extracellular matrix’, ‘cell junction’, ‘protein binding’ and ‘guanosine triphosphatase activity’. Several significant pathways were identified, including ‘focal adhesion’ and ‘extracellular matrix-receptor interaction pathway’. This study provides evidence that there are differences in genome-wide DNA methylation between ULs in menopausal women with and without POP, and that epigenetic mechanisms may partly contribute to POP pathogenesis.
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影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
15.9
作者：
Connell, Kathleen A.;Guess, Marsha K.;Taylor, Hugh S.
通讯作者：
Taylor, Hugh S.
DOI：
10.1111/1471-0528.12075
发表时间：
2013-01-01
影响因子：
5.8
作者：
Glazener, C.;Elders, A.;Wilson, D.
通讯作者：
Wilson, D.
影响因子：
120.7
作者：
Nygaard, Ingrid;Barber, Matthew D.;Burgio, Kathryn L.;Kenton, Kimberly;Meikle, Susan;Schaffer, Joseph;Spino, Cathie;Whitehead, William E.;Wu, Jennifer;Brody, Debra J.
通讯作者：
Brody, Debra J.
影响因子：
3.7
作者：
Rao S;Lang J;Zhu L;Chen J
通讯作者：
Chen J