Mahnaz Rezaei1,2, Fatemeh Eskandari1,2, Abbas Mohammadpour-Gharehbagh1,2, Mahdiyeh Harati-Sadegh3,4, Batool Teimoori5, Saeedeh Salimi1,2. 1. a Department of Clinical Biochemistry, School of Medicine , Zahedan University of Medical Sciences , Zahedan , Iran. 2. b Cellular and Molecular Research Center , Zahedan University of Medical Sciences , Zahedan , Iran. 3. c Department of Genetics, Fars Science and Research Branch , Islamic Azad University , Marvdasht , Iran. 4. d Department of Genetics, Marvdasht Branch , Islamic Azad University , Marvdasht , Iran. 5. e Department of Obstetrics and Gynecology, School of Medicine , Zahedan University of Medical Sciences , Zahedan , Iran.
Abstract
PURPOSE: 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. METHODS: 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). RESULTS: 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]. CONCLUSIONS: An association was found between hypo-methylation of the miR-34a promoter and PE and PE severity.
PURPOSE: 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. METHODS: 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). RESULTS: 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]. CONCLUSIONS: An association was found between hypo-methylation of the miR-34a promoter and PE and PE severity.