Hypomethylation of the PGF gene and lower PLGF expression are associated with a higher risk of preeclampsia

Introduction: Preeclampsia is a global health problem that complicates 2-8% of pregnancies and contributes to 18% of maternal deaths worldwide. Recent study showed a potential role of epigenetic modification in the pathogenesis of preeclampsia. This study aims to determine whether hypomethylation of the placental growth factor (PGF) gene and lower placental growth factor (PLGF) expression in placental tissue will result in a higher risk of preeclampsia. Methods: This observational study involved 30 pregnant women with preeclampsia (cases) and 30 normotensive healthy pregnant women (controls). After labor, a 2 cm3 fresh placental tissue sample was obtained from the chorion part in the central area of umbilical cord insertion. The methylation level of the PGF gene was measured using polymerase chain reaction (PCR), and PLGF expression was measured using enzyme-linked immunosorbent assay (ELISA). The optimal cut-off was obtained using a Receiver Operating Curve (ROC) analysis. Then, a multivariate analysis was performed to determine the risk factors of preeclampsia. Results: Preeclamptic women had significantly lower DNA methylation on the PGF gene (27.89±19.70% vs. 58.95±22.98%; p<0.001) and lower placental PLGF expression (9.50±20.01 vs. 51.29±108.25 pg/ml, p<0.001) compared to normotensive healthy pregnant women. After adjusting to the confounding factors, it was found that hypomethylation of the PGF gene (<24.98%) significantly increased the risk of preeclampsia (AOR 21.18; CI95% 2.49-179.72; p=0.005). A lower PlGF expression (≤ 4.05 pg/ml) also significantly increased the risk of preeclampsia (AOR 12.55; CI95% 1.95-80.83; p=0.008). Conclusion: This study showed the importance of DNA hypomethylation of the PGF gene promoter in down-regulating PlGF expression, which has a vital role in preeclampsia. Therefore, this suggests that epigenetic modification of the PGF gene may serve as a potential therapeutic target in preventing preeclampsia in high-risk pregnant women.