Preeclampsia (PE), a form of pregnancy-induced hypertension, is believed to have a genetic component with both the mother and the fetus contributing to the risk of PE. Although numerous studies have been conducted to investigate maternal genetic contributions to PE susceptibility, most previous studies have failed to consider the role of fetal genotype. Our long-term goal, to be pursued in future studies, is to conduct a large-scale candidate gene study to examine the roles of maternal and fetal genotypes and maternal-fetal gene-gene (GxG) interaction in PE susceptibility. Among the candidate genes to be examined, we propose to examine a promising class of genes that has been previously overlooked: genes involved in vascularization and development of the placenta. To date, no placentation genes have been included in candidate gene studies, and very little is known about polymorphism in these genes. ? ? Specifically, we propose a feasibility study to examine several genes involved in placentation (HAND1, HASH2, GCM1, HIF-1alpha and TGFbeta3) and angiogenesis (VEGF, sFLT1, PGF), and one gene involved in utero-placental blood pressure regulation (MAO-A). We propose to resequence the coding and regulatory regions of these genes to identify all common variants, determine allele and haplotype frequencies and attempt to generate preliminary data linking polymorphism in these genes to PE risk. We will accomplish this aim by conducting a pilot case-control study of women with a history of PE (during their first pregnancy with a specific partner) and controls with a normotensive pregnancy history, matched on maternal age, race, gestational age and year/month of delivery. We intend to identify and recruit 120 case/child pairs and 240 control/child pairs using the delivery logs from the Los Angeles County/University of Southern California (LAC+USC) Women's and Children's Hospital. Finally, because the patient population of LAC+USC is predominantly Hispanic, and because Hispanics are an ethnically admixed population, we will also determine the extent of population stratification in this population to assess whether stratification is likely to lead to biased gene-disease associations. While the likely severity of such bias has been debated in the epidemiologic literature, there have been no studies to assess the extent of this problem in Hispanics, one of the populations that is most likely to be affected. ? ?
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| Shahabi, Ahva; Wilson, Melissa L; Lewinger, Juan Pablo et al. (2013) Genetic admixture and risk of hypertensive disorders of pregnancy among Latinas in Los Angeles County. Epidemiology 24:285-94 |
| Wilson, Melissa L; Desmond, Daniel H; Goodwin, T Murphy et al. (2009) Maternal and fetal variants in the TGF-beta3 gene and risk of pregnancy-induced hypertension in a predominantly Latino population. Am J Obstet Gynecol 201:295.e1-5 |
