RNA Biomarkers

Placental RNA analyzed in maternal plasma permits rapid screening of novel biomarkers including biomarkers not accessible by antibody based assays. This includes transcription factors, non-coding RNA (ncRNA), epigenetic features, as well as genes functionally or genetically linked with preeclampsia. Review of genes with placental expression in the Human SymAtlas and comparison with proven qualifiers, has revealed a large number of RNA biomarkers that may be useful for the presymptomatic detection in first trimester of pregnancy-associated diseases with placental origin and/or dysfunction such as pregnancy-induced hypertension without or with proteinuria (preeclampsia), and intrauterine growth restriction.

A laser microdissection approach has enabled the identification of novel mRNAs and ncRNAs that were misexpressed by various trophoblast subpopulations in severe preeclampsia (Gormley et al. 2017). Many of the newly identified dysregu- lated molecules might have clinical utility as biomarkers of severe preeclampsia.

Genes Associated with Preeclampsia

Polymorphisms of the adiponectin gene show a weak, but statistically significant, haplotype association with susceptibility to preeclampsia in Finnish women (Saarela et al. 2006). Although many genetic screens in multiple populations have been performed, only two preeclampsia susceptibility genes (ACVR2A, STOX1) have been identified within confirmed regions with significant genome-wide linkage (van Dijk and Oudejans 2011). STOX1 genotype has been shown to directly limit first trimester extravillous trophoblast invasion, the earliest hallmark of preeclampsia. The authors have described upstream regulation and downstream effector genes of the transcription factor STOX1 and proposed a model combining the cell type-specific and allele-specific effects of STOX1 including intrinsic effects (differential CpG island methylation) and extrinsic effects (regulation of effector genes).

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