Abstract 15439: Molecular Basis for Racial Disparity in the Etiology of Pre-Eclampsia
Introduction: Pre-eclampsia (PE) affects 5-8% of pregnancies worldwide and is a significant source of perinatal morbidity and mortality. PE results in hypertension and proteinuria after 20 weeks of pregnancy whose increasing severity leads to premature delivery. Mechanisms underlying PE are poorly understood as are risk factors mediating observed racial disparity. The developmental gene Nkx2.5 is expressed in trophoblast cells and abnormal amnions are observed in mice bearing null Nkx2.5 mutations.
Hypothesis: We therefore hypothesized that Nkx2.5 and Nkx2.5-related gene expression would vary in placentae from normal vs. PE pregnancies.
Methods: We used qPCR and immunohistochemistry to analyze placental samples from 30 patients with early onset and severe pre-eclampsia (PE).
Results: We have found in this preliminary study that there is a strong correlation between early onset severe PE (EOSPE) and high levels of placental Nkx2.5 expression, with greater prevalence in U.S. Caucasian Americans (CA), as compared to U.S. African Americans (AA). We additionally found a significant and positive correlation between high Nkx2.5 mRNA expression levels and high levels of mRNA encoding a significant marker and mediator of PE and PE severity, sFlt-1; this correlation is statistically significant in CA but not AA. Additionally, we found that two other Nkx2.5 target genes, Ccdc117 and the stress response factor Xbp-1 show elevated expression in either CA (Ccdc117) or AA (Xbp-1) PE patients with high Nkx2.5 expression. Nkx2.5 and its downstream targets are expressed in syncytiotrophoblast of EOSPE placenta, the site of sFlt-1 synthesis and a focus of PE pathogenesis.
Conclusions: Abnormal Nkx2.5 and Nkx2.5 target gene regulation potentially underlies a novel PE mechanism identifying a subpopulation of patients in racially disparate fashion.
- © 2013 by American Heart Association, Inc.