Role of oxysterol 4β-hydroxycholesterol and liver X receptor alleles in pre-eclampsia

TL;DR

This study explores the role of oxysterol 4β-hydroxycholesterol and liver X receptor alleles in pre-eclampsia but finds limited direct associations with blood pressure or disease risk.

Contribution

The study evaluates novel associations between oxysterol 4β-hydroxycholesterol, liver X receptor genetic variants, and pre-eclampsia using a Finnish cohort and FinnGen data.

Findings

Plasma 4β-hydroxycholesterol levels were inversely correlated with maternal body mass index.

LXR target genes APOD, SCARB1, TGM2, and LPCAT3 showed differential expression in pre-eclamptic versus normal pregnancies.

No significant associations were found between LXR genetic variants and pre-eclampsia or blood pressure regulation.

Abstract

Liver X receptors (LXRs) are expressed in placenta and may be associated with pre-eclampsia (PE). Oxysterols act as agonists for LXRs. We recently proposed a new blood pressure-regulating circuit with oxysterol 4β-hydroxycholesterol (4βHC) acting as a hypotensive factor via LXRs.

This study investigated the association between maternal plasma 4βHC, blood pressure (BP) indices, placental expression of LXR target genes, and patient characteristics using data from the Finnish Genetics of Pre-Eclampsia Consortium (FINNPEC) cohort. Plasma samples of 144 women with PE and 38 healthy pregnant controls as well as 44 PE and 40 control placental samples were available. In addition, genetic data from the FinnGen project was utilized to explore the associations of LXR alleles with PE and pregnancy hypertension.

There were no significant associations between 4βHC and BP or maternal and perinatal characteristics in FINNPEC cohort. However, plasma 4βHC was inversely correlated with the maternal body mass index. There were no associations with the genetic variants of LXRs with PE in FinnGen. LXR target genes APOD, SCARB1, TGM2, and LPCAT3 were expressed differently between PE and normal pregnancies in placental samples of FINNPEC.

Our results demonstrate that plasma 4βHC and genetic LXR variants do not play a major role in PE and BP regulation during pregnancy. However, key LXR target genes involved in lipid metabolism were expressed differently in normal and PE pregnancies. Further research is needed to understand the complexities of oxysterols, LXRs, and their potential contributions to placental function and pregnancy outcomes.

Plasma 4βHC and genetic LXR variants do not play a major role in PE and BP regulation during pregnancy.Plasma 4βHC was inversely correlated with the maternal body mass index.The expression of LXR target genes APOD, TGM2, SCARB1 and LPCAT3 had significant difference between the PE and normal pregnancies.

Plasma 4βHC and genetic LXR variants do not play a major role in PE and BP regulation during pregnancy.

Plasma 4βHC was inversely correlated with the maternal body mass index.

The expression of LXR target genes APOD, TGM2, SCARB1 and LPCAT3 had significant difference between the PE and normal pregnancies.

Figures