Abstract
Several studies have linked maternal asthma, excess BMI, and low vitamin D status with increased risk of Preeclampsia (PE) development. Given prior evidence in the literature and our observations from the subjects in the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we hypothesized that PE, maternal asthma, vitamin D insufficiency, and excess body mass index (BMI) might share both peripheral blood and placental gene signatures that link these conditions together. We used samples collected in the VDAART to investigate relationships between these four conditions and gene expression patterns in peripheral blood obtained at early pregnancy. We identified a core set of differentially expressed genes in all comparisons between women with and without these four conditions and confirmed them in two separate sets of samples. We confirmed the differential expression of the shared gene signatures in the placenta from an independent study of preeclampsia cases and controls and constructed the preeclampsia module using protein–protein interaction networks. CXC chemokine genes showed the highest degrees of connectivity and betweenness centrality in the peripheral blood and placental modules. The shared gene signatures demonstrate the biological pathways involved in preeclampsia at the pre-clinical stage and may be used for the prediction of preeclampsia.
Highlights
Several studies have linked maternal asthma, excess body mass index (BMI), and low vitamin D status with increased risk of Preeclampsia (PE) development
We identified a core set of differentially expressed gene signatures associated with each study condition that was confirmed in the early pregnancy of separate sets of pregnant women (Fig. 1)
The PE signatures were confirmed in early pregnancy samples from an independent set of pregnant women and refined according to maternal risk factors, i.e., asthma, excess BMI, and insufficient vitamin D status at early pregnancy
Summary
Several studies have linked maternal asthma, excess BMI, and low vitamin D status with increased risk of Preeclampsia (PE) development. Given prior evidence in the literature and our observations from the subjects in the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we hypothesized that PE, maternal asthma, vitamin D insufficiency, and excess body mass index (BMI) might share both peripheral blood and placental gene signatures that link these conditions together. Given prior evidence in the literature and from the VDAART cohort, we hypothesized that PE, maternal asthma, vitamin D insufficiency, and excess BMI in early pregnancy might share dysregulated biological pathways in peripheral blood and placenta. To investigate this hypothesis, we conducted a microarray differential gene expression study in a nested case–control subset of pregnant women participating in the VDAART trial. We performed a network-based analysis of these overlapping gene signatures to visualize the commonality between these conditions at the molecular level
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