High-Throughput Methylome Analysis Reveals Differential Methylation During for Early and Late Onset Preeclampsia for Mothers and Their Newborn Children
Preeclampsia is a hypertensive disorder of pregnancy that affects approximately 2-5% of all pregnancies, contributes to 4 of the top 10 causes of pregnancy-related deaths, and remains a long-term risk factor for cardiometabolic diseases. Yet, little is still known about the molecular mechanisms that lead to this disease. There is evidence that some cases have a genetic cause. However, it is well appreciated that harmful factors in the environment, such as poor nutrition, stress, and toxins, may lead to epigenetics changes that can contribute to this disease. DNA methylation is one of the epigenetic modifications known to be fairly stable and impact gene expression. Using DNA from buccal swabs from pregnant women, we analyzed global DNA methylation among pregnancies complicated by preeclampsia at <32 weeks (early) and >37 weeks (late) against uncomplicated pregnancies, as well as newborns from these pregnancies. We found significant differentially methylated regions between pregnancies complicated by preeclampsia compared to normal pregnancies adjacent or within genes that are important for placentaton, embryonic development, cell adhesion, inflammation (e.g., the cadherin pathway) and many reported to be expressed in tissues relevant to preeclampsia (i.e. brain, heart, kidney, and placenta). As this study was performed on DNA extracted from cheek swabs, this opens the way to future studies in different tissues, aimed at identifying possible biomarkers of risk and early detection, develop targeted interventions, and reduce the progression of this life-threatening disease. Overall design: The study included 6 groups: 1) Early-preeclampsia mothers (>32 weeks) N=10; 2) Children from early-preeclampsia mothers N=10; 3) Late-preeclampsia mothers (>37 weeks) N=9; 4) Children from late-preeclampsia mothers N=9; 5) Normal pregnancy mothers N=10; 6) Children from normal pregnancy mothers N=9