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Title: The Pathophysiology of Preeclampsia: An Analysis of Genetic, Biological, and Social Factors
Authors: Peifer, Sophia
Advisors: Murphy, Coleen
Department: Molecular Biology
Certificate Program: Global Health and Health Policy Program
Class Year: 2021
Abstract: Maternal mortality rates in the United States continue to be among the highest in the world, and top among developed countries. Preeclampsia (PE) complicates around 2 to 8% of all pregnancies, but the pathophysiology of the condition is not yet well understood. Various biological processes are implicated in preeclampsia including epigenetic age acceleration, the immune system, abnormal placentation, thrombosis, and the renin-angiotensin system. Preeclampsia has a high comorbidity with preterm birth, intrauterine growth restriction (IUGR), and stroke later in life, and the underlying mechanisms which link these conditions are yet to be elucidated. In this study, I used publicly available GWAS datasets on preeclampsia, preterm birth, early preterm birth, maternal effects on birth weight, and stroke to investigate significant SNPs and their potential pleiotropic effects. Suggestive SNPs from these datasets were then analyzed for functional association with genes. Furthermore, I conducted a differential expression analysis using RNA sequencing data from patients with preeclampsia and healthy controls and found differential expression of 23 genes. Pathway analysis of these genes revealed that circulatory system development, blood vessel morphogenesis, the Wnt/β-Catenin pathway, and the JAK-STAT pathway are involved in preeclampsia pathophysiology. Specifically, EYA1, MEOX2, PTPN11, COL8A1, GSK3B, TCF7L2, SH2B3, LEPR, and ADAM12 genes were implicated in the differential expression and pathway analyses. The identification of genes related to preeclampsia provides insight into its physiology and could aid the development of future therapeutics or genetic risk screenings. ADAM12, a potential biomarker for genetic screenings of stroke and preeclampsia risk, HIF-1α inhibitors, JAK-STAT inhibitors, and resveratrol supplements should be further investigated as therapeutics since they are associated with the identified pathways.
Type of Material: Princeton University Senior Theses
Language: en
Appears in Collections:Molecular Biology, 1954-2021

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