Genetic Variants Associated With Preeclampsia and Maternal Serum SFLT1 Levels

Overview

Journal Hypertension

Date 2024 Dec 26

PMID 39723542

Authors

Jasmine A Mack

Ulla Sovio

Felix R Day

Francesca Gaccioli

Emma Cook

Nadua Bayzid

Marius Cotic

Nathan Dunton

Gaganjit Madhan

Alison Motsinger-Reif

John R B Perry

D Stephen Charnock-Jones

Gordon C S Smith

Affiliations

Soon will be listed here.

Abstract

Background: Elevated maternal serum sFLT1 (soluble fms-like tyrosine kinase 1) has a key role in the pathophysiology of preeclampsia. We sought to determine the relationship between the maternal and fetal genome and maternal levels of sFLT1 at 12, 20, 28, and 36 weeks of gestational age (wkGA).

Methods: We studied a prospective cohort of nulliparous women (3968 mother-child pairs). We related maternal and fetal genotype to the adjusted sFLT1 score and sFLT1:placental growth factor (PlGF) ratio score at each wkGA and the change in the score between 28 and 36 wkGA (Δ36-28). We studied genetic variants from a previous fetal genome-wide association study of preeclampsia and an externally defined polygenic score from a maternal genome-wide association study of preeclampsia.

Results: Four variants from the fetal preeclampsia genome-wide association study were positively associated with sFLT1 and sFLT1:PlGF score at 36 wkGA, and enhancer single-nucleotide polymorphisms were associated with increased Δ36-28 of sFLT1. The associations were specific for the fetal genome or stronger for the fetal than the maternal genome. An increased risk of preeclampsia based on the maternal polygenic score for preeclampsia was associated with lower levels of sFLT1 and sFLT1:PlGF ratio in the first trimester and a greater Δ36-28 for sFLT1.

Conclusions: The current data are consistent with a causal association between sFLT1 released by the placenta in late pregnancy and the pathophysiology of preeclampsia. The data are also consistent with maternal components to the protective effect of high sFLT1 in the first trimester and the rise in third-trimester sFLT1 levels and preeclampsia.

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