GENETIC AND NONGENETIC RISK FACTORS OF PREECLAMPSIA

Swedish Medical Center, First Hill, Seattle WA

Investigators

Linked publications & trials

Abstract

DESCRIPTION: (Adapted from Investigator's Abstract) Preeclampsia, the most common complication of pregnancy and a leading cause of maternal mortality world-wide, is an important cause of preterm delivery, fetal growth retardation and perinatal mortality. Pregnancies complicated by preeclampsia are associated with hyperlipidemia. Diffuse endothelial dysfunction associated with preeclampsia is thought to be caused by blood-borne products. It has been hypothesized that plasma lipids may have direct adverse effects on endothelial function in pregnancy. Although approximately 50% of the inter-individual variation in plasma lipids are thought to be genetically determined, no one has systematically evaluated the relationship between preeclampsia and genetic markers known to be associated with dyslipidemia and cardiovascular disorders in non-pregnant individuals. Given 1) evidence of a genetic tendency towards susceptibility for preeclampsia; 2) the excess risk of preeclampsia in women with metabolic disorders known to have a strong genetic component; 3) available data suggesting that preeclamptics are at increased risk of developing hypertension or coronary heart disease later in life as compared to women with normotensive pregnancies; and 4) the emerging importance of genetic and environmental interactions in determining risk of complex phenotypes (e.g., circulating triglyceride levels) and predicting risk of complex metabolic disorders (e.g., hypertension, diabetes), the investigators propose to conduct a multi-center, hospital-based, case-control study to examine the hypothesis that the apolipoprotein E (ApoE) polymorphism (an important determinant of variation in lipid levels) plays a role in determining risk of preeclampsia. Risk associated with non-genetic determinants of dyslipidemia, such as fat intake, exercise and obesity will also be assessed. To accomplish these aims, they will conduct in-person interviews with, and collect blood specimens from, 400 women with preeclampsia and 400 normotensive pregnant women. Blood specimens will be processed and stored at -70 degrees C. until ApoE genotyping is performed. Statistical analysis will focus on determining risk of preeclampsia for those women carrying the ApoE2 and ApoE4 alleles, respectively, as compared to women who are homozygous ApoE3/E3. In addition to addressing the primary aim, the investigators note that data collected for the proposed study will allow for an evaluation of the association between preeclampsia and other putative genetic and non-genetic risk factors. They further state that clinical applications of study findings may result in early identification of high risk subjects and effective interventions.