The Human Placenta Project

Genetic variants and placental function

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Our research group in the NIDDK Intramural Research Program has investigated the risk of APOL1 genetic variants in many types of kidney diseases, including focal segmental nephrosclerosis, HIV-associated nephropathy, and hypertension-attributed kidney disease. Together, these disease account for much of the excess chronic kidney disease risk among African-Americans.

We are accumulating evidence that APOL1 risk variants carried by the fetus and fetal-maternal APOL1 mismatch can be a risk for preeclampsia, as shown in clinical studies (Reidy, Am J Hum Genet, 2018; Hong, Am J Kid Dis, 2020) and in APOL1-transgenic mice. Further, there is accumulating evidence that particular placental cell types play particular roles, including trophoblasts in early placentation (with implications for preeclampsia) and Hofbauer cells in promoting inflammation (with implication for vertical transmission of infection to the fetus).

We propose the establishment of a biobank for frozen human placental tissues, accompanied by a database containing associated genetic and clinical information. This could be of great benefit to drive forward this clinically-important field. This biobank would enable clinical studies that could profile multi-omic data (transcriptome, proteome, metabolome and others) at single-cell resolution in normotensive pregnancies and in pregnancies complicated by pre-eclampsia and other placental abnormalities. This biobank could also facilitate studies to characterize the roles of particular genetic variants in the pathophysiology of preeclampsia, identify mechanistic pathways, and develop clinical tests to identify mothers at increased risk for pre-eclampsia.



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Idea No. 152