Racial discrepancies in placental gene expressions between Black and White healthy and preeclampsia patients of equivalent BMI and blood pressure in a Southeastern USA cohort

Preeclampsia is a devastating hypertensive disorder of pregnancy that afflicts between 5-10% of pregnancies in the US, with a higher prevalence in the southern regions of the United States. Black pregnant women are disproportionally at higher risk for preeclampsia onset and severity of disease than other racial groups, including White women. Although this has been recognized in the maternal fetal medicine literature for many years, the underlying mechanism(s) for this racial disparity are unclear. One confounding issue with many studies of racial discrepancies in pregnant women is differences in comorbidities between racial groups. In our current study we were able to obtain a cohort of patients of self-identifying Black or White race that were overall matched for BMI, blood pressure, gestational age and parity and we hypothesized that genetic and placental markers of preeclampsia would be highest in our preeclampsia Black patients compared to healthy patients or White preeclampsia patients. We collected placenta tissue from this cohort of deliveries in Augusta, GA from both healthy and preeclamptic Black and White women (n=13-15). We measured expressions of several preeclampsia-implicated genes, as well as performed a placental morphological analysis and RNA sequencing of a subset of samples. Contrary to our hypothesis, our results from ddPCR analysis of genes associated with preeclampsia risk demonstrated that leptin, preproendothelin-1 (PPET-1) endothelial converting enzyme-1 (ECE-1) and soluble FMS-like tyrosine kinase-1 (sFlt-1) were higher in White preeclamptic women than in Black preeclamptic women. Our RNA sequencing analysis revealed that 136 genes significantly differed between White and Black normal pregnant patients, 288 genes differed between Black healthy and Black preeclampsia patients, while a striking 2394 genes significantly differed between White healthy and White preeclampsia patients and 2346 genes differed between White and Black preeclampsia patients. Placental histology analysis revealed that Black preeclampsia patients demonstrated a lower scoring of morphological pathologies associated with preeclampsia compared to White preeclampsia patients. Collectively, these data indicate that genetic predisposition to preeclampsia in White patients in the placenta differs greatly to that of Black patients, and that placental changes may be more subtle in Black patients that are at high risk for preeclampsia.