Ji Fei, Yang Xinhua, He Yan, Wang Hui, Aili Aixingzi, Ding Yan
Department of Gynecology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, Urumqi, 830054, China.
Department of Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 201204, China.
J Assist Reprod Genet. 2017 Mar;34(3):409-415. doi: 10.1007/s10815-016-0862-6. Epub 2017 Jan 10.
Differential methylation of both HOXA10 and catechol-O-methyltransferase (COMT) has been reported in different endometrium disorders, and the two genes are linked through the estrogen pathway. The current study investigates the DNA methylation of HOXA10 and COMT in ectopic and eutopic endometrial tissues and its correlation with and the occurrence of endometriosis in women from Xinjiang province in China.
In the current study, 120 patients with endometriosis were recruited from our hospital between January 2011 and June 2014. The DNA methylation sites of HOXA10 and COMT were detected using a DNA methylation array. The methylation levels of specific sites were compared between ectopic and eutopic endometrial tissues via pyrosequencing.
Five differentially expressed CpGs were localized in the promoter region of the COMT gene and expressed significantly higher in the ectopic endometrium than the eutopic endometrium (P < 0.001). Two out of the five differentially expressed CpGs in the HOXA10 gene located in the promoter region were both significantly lower (nearly half) in the ectopic endometrium than the eutopic endometrium (P < 0.001).
To summarize, significant differential methylation of HOXA10 and COMT promoter regions was found between the ectopic and eutopic endometrial tissues. This is the first study investigating the methylation of HOXA10 and COMT genes and their linkage to endometriosis in Chinese patients.
已有报道称,在不同的子宫内膜疾病中,HOXA10和儿茶酚-O-甲基转移酶(COMT)均存在差异甲基化,且这两个基因通过雌激素途径相联系。本研究调查了中国新疆地区女性异位和在位子宫内膜组织中HOXA10和COMT的DNA甲基化情况,及其与子宫内膜异位症发生的相关性。
在本研究中,2011年1月至2014年6月期间从我院招募了120例子宫内膜异位症患者。使用DNA甲基化芯片检测HOXA10和COMT的DNA甲基化位点。通过焦磷酸测序比较异位和在位子宫内膜组织中特定位点的甲基化水平。
五个差异表达的CpG定位于COMT基因的启动子区域,在异位子宫内膜中的表达明显高于在位子宫内膜(P < 0.001)。位于启动子区域的HOXA10基因中五个差异表达的CpG中有两个在异位子宫内膜中的表达均明显低于在位子宫内膜(几乎减半)(P < 0.001)。
综上所述,在异位和在位子宫内膜组织之间发现了HOXA10和COMT启动子区域明显的差异甲基化。这是首次在中国患者中研究HOXA10和COMT基因的甲基化及其与子宫内膜异位症的联系。