Promoter hypomethylation of COMT in human placenta is not associated with the development of pre-eclampsia
Promoter hypomethylation of COMT in human placenta is not associated with the development of pre-eclampsia
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人胎盘中 COMT 启动子低甲基化与先兆子痫的发生无关
DOI：
10.1093/molehr/gaq092
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发表时间：
2011-03-01
影响因子：
4
通讯作者：
Zhao, Xinzhi
中科院分区：
文献类型：
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作者：
Zhao, Arman;Cheng, Yan;Zhao, Xinzhi
儿茶酚-O-甲基转移酶（COMT）基因的破坏已被证明与先兆子痫（PE）有关。为了研究COMT基因的两个启动子是否在PE患者中受到甲基化的差异调节，我们分析了从PE妇女和正常妊娠妇女的胎盘（病例n = 16;对照n = 21）、母体外周血（病例n = 4;对照n = 6）和脐带血（病例n = 8;对照n = 8）提取的基因组DNA。亚硫酸氢盐测序鉴定了胎盘、母体外周血和脐带血样品（PE和对照）中主要未甲基化的MB-COMT启动子。随后的定量MassArray数据证实了胎盘中S-COMT启动子的显著组织特异性低甲基化（平均值= 28.6%），与血液样品中的密集甲基化模式（平均值= 74.5%，P < 0.001）相比，与测序数据一致。然而，无论是在胎盘还是在血液样本中，病例和对照之间均未发现PE特异性甲基化差异。此外，没有一个临床特征对S-COMT启动子的甲基化状态有影响。本研究不支持COMT启动子甲基化调控与PE之间的因果关系。然而，所观察到的胎盘特异性S-COMT启动子可能是早期预测母体血浆中PE的潜在标志物，尽管这仍有待进一步评估。
Disruption of the Catechol-O-methyltransferase (COMT) gene has been shown to be involved in pre-eclampsia (PE). To investigate whether two promoters of the COMT gene are differentially regulated by methylation in PE patients, we have analyzed the genomic DNA extracted from placenta (cases n = 16; controls n = 21), maternal peripheral blood (cases n = 4; controls n = 6) and umbilical cord blood (cases n = 8; controls n = 8) of women with PE and women with normal pregnancy. Bisulfite sequencing identified the predominantly unmethylated MB-COMT promoter in placenta, maternal peripheral blood and umbilical cord blood samples (PE and control). Subsequent quantitative MassArray data confirmed a significant tissue-specific hypomethylation of the S-COMT promoter in placenta (mean = 28.6%) when compared with its densely methylated patterns in blood samples (mean = 74.5%, P < 0.001), consistent with the sequencing data. However, no PE-specific methylation difference was found between cases and controls either in placenta or in blood samples. Moreover, none of the clinical characteristics had an effect on the methylation status of the S-COMT promoter. This study does not support a causal link between methylation regulation of COMT promoters and PE. However, the observed placenta-specific S-COMT promoter may be a potential marker for early prediction of PE in maternal plasma, although this remains to be further evaluated.