This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. About 6% of pregnancies are complicated by hypertension and proteinuria, commonly termed preeclampsia. Preeclampsia/eclampsia (P/E) is a risk factor for both maternal and neonatal morbidity and mortality. Although some risk factors have been identified, the underlying cause of P/E remains unknown. P/E is more common among women in disadvantaged socio-economic populations, with incidences of up to 30%. The incidence of P/E in this American Indian (AI) community is unknown, but data suggests that it is at least 5.4%. Research in non-Indian populations has related the risk of P/E to genetic changes influencing the blood clotting cascade (factor V Leiden), abnormalities of plasminogen activating inhibitor-1 (PAI-1)), lipid abnormalities (lipoprotein lipase) and renal physiology (mineralocorticoid receptor and renin genes). The PAI-1 gene is associated with insulin resistance (common in AI populations), amenable to treatment with metformin, and thus of additional importance. This proposal will collect DNA samples on specialized blotting paper, from about 100 cases and 200 matched controls. Genetic polymorphisms of possible functional significance will be genotyped using PCR amplification, restriction endonuclease digestion and analysis of products on electrophoresis gels. The possible association of risk genotypes in this population to P/E will be examined. Approximately 560 additional participants will be enrolled from prenatal clinics for a prospective analysis. Information about the prevalence of these genetic polymorphisms and their possible relevance to P/E is not otherwise available and is useful not only to better understand the underlying pathophysiology of P/E;but also for public health and clinical use in judging the utility of genetic screening tests in this particular population and perhaps other related AI communities.
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