Rezaei Mahnaz, Eskandari Fatemeh, Mohammadpour-Gharehbagh Abbas, Harati-Sadegh Mahdiyeh, Teimoori Batool, Salimi Saeedeh
a Department of Clinical Biochemistry, School of Medicine , Zahedan University of Medical Sciences , Zahedan , Iran.
b Cellular and Molecular Research Center , Zahedan University of Medical Sciences , Zahedan , Iran.
Clin Exp Hypertens. 2018 Mar 20:1-5. doi: 10.1080/10641963.2018.1451534.
PE is a pregnancy-specific complication, which genetic and epigenetic factors play key roles in its pathogenesis. DNA methylation is a main epigenetic alteration with important roles in gene regulation. Micro RNAs (miRNAs) as another member of epigenetic machinery regulate the gene expression and involve in different biological pathways including apoptosis and placental development. Therefore, the present study performed to assess the association between miRNA-34a promoter methylation and PE susceptibility.
The placenta of 104 PE pregnant women and 119 normotensive pregnant women were collected after delivery. The methylation status of the miRNA-34a promoter was assessed using Methylation Specific PCR (MSP).
The frequency of the hemi-methylated (MU) miR-34a promoter was significantly lower in PE women compared to the controls (17.3 vs. 29.4%) (OR, 0.45 [95% CI, 0.2-0.9], P = 0.016). The overall methylation rate was 23.1% in PE women and 41.2% in the control group and was significantly lower in PE women (OR, 0.4 [95% CI, 0.2-0.8], P = 0.004). The frequency of hemi-methylated (MU) and overall methylated (MU+MM) promoter of miR-34a gene was significantly lower in severe PE but not in mild PE women compared to the controls [(OR, 0.3 [95% CI, 0.1-0.8], P = 0.02) and (OR, 0.3 [95% CI, 0.1-0.7], P = 0.009), respectively]. There was an association between hemi-methylated (MU) and overall methylated (MU+MM) promoter and late onset PE [(OR, 0.4 [95% CI, 0.2-0.9], P = 0.03) and (OR, 0.4 [95% CI, 0.2-0.8], P = 0.01), respectively].
An association was found between hypo-methylation of the miR-34a promoter and PE and PE severity.
子痫前期是一种妊娠特异性并发症，遗传和表观遗传因素在其发病机制中起关键作用。DNA甲基化是一种主要的表观遗传改变，在基因调控中具有重要作用。微小RNA（miRNA）作为表观遗传机制的另一个成员，可调节基因表达，并参与包括细胞凋亡和胎盘发育在内的不同生物学途径。因此，本研究旨在评估miRNA - 34a启动子甲基化与子痫前期易感性之间的关联。
收集104例子痫前期孕妇和119例血压正常孕妇产后的胎盘。采用甲基化特异性PCR（MSP）评估miRNA - 34a启动子的甲基化状态。
与对照组相比，子痫前期妇女中半甲基化（MU）miRNA - 34a启动子的频率显著降低（17.3%对29.4%）（OR，0.45 [95% CI，0.2 - 0.9]，P = 0.016）。子痫前期妇女的总体甲基化率为23.1%，对照组为41.2%，子痫前期妇女的总体甲基化率显著更低（OR，0.4 [95% CI，0.2 - 0.8]，P = 0.004）。与对照组相比，重度子痫前期妇女中miRNA - 34a基因半甲基化（MU）和总体甲基化（MU + MM）启动子的频率显著降低，但轻度子痫前期妇女中未降低[分别为（OR，0.3 [95% CI，0.1 - 0.8]，P = 0.02）和（OR，0.3 [95% CI，0.1 - 0.7]，P = 0.009）]。半甲基化（MU）和总体甲基化（MU + MM）启动子与晚发型子痫前期之间存在关联[分别为（OR，0.4 [95% CI，0.2 - 0.9]，P = 0.03）和（OR，0.4 [95% CI，0.2 - 0.8]，P = 0.01）]。
发现miRNA - 34a启动子低甲基化与子痫前期及其严重程度之间存在关联。
