64-OR

Abstract

Objectives Pre-eclampsia (PE) affects 5-8% of pregnancies, and factors causing PE and mediating observed racial disparity are poorly understood. The cardiovascular gene Nkx2-5 is expressed in trophoblast cells and abnormal amnions are observed in mice Nkx2-5 mutant mice. We assessed Nkx2-5-related gene expression in placenta from normal and early onset and severe pre-eclampsia (EOSPE) pregnancies. Methods IHC and qPCR assay of Nkx2.5 and target gene expression in normal term and EOSPE placenta. Results Nkx2-5 is highly expressed in a subset of early EOSPE placentae, and is highly correlated with expression of the PE marker sFlt-1, and with an RNA splicing factor, Sam68. These correlations are significant in Caucasian, but not African American women. siRNA knockdown of Sam68 significantly impacts sFlt-1 expression in vitro, supporting a hypothesis that Nkx2-5 impacts EOSPE severity via upregulation of Sam68 and increased sFlt-1 expression. Other Nkx2-5 targets related to metabolic stress responses are also differentially activated in between Caucasians and African American women with EOSPE. Conclusions Nkx2-5 may play a direct role in the genesis of PE via regulation of Sam68/sFlt-1, and serve as a common link to two other stress-related modifiers of EOSPE. Disclosures E.R. Rivers: None. A.J. Horton: None. C.D. Clark: None. E.G. Favre: None. K.M. Senf: None. A.F. Hawk: None. E.Y. Chang: Consultant, Commercial Interest: Alere PETRA study, Hologic, Inc. C.J. Robinson: None. K. Lee: None.