Genetic Approaches in Preeclampsia

Abstract

Preeclampsia (PE) is a serious hypertensive disorder that affects up to 8% of all pregnancies annually. An established risk factor for PE is family history, clearly demonstrating an underlying genetic component to the disorder. To date, numerous genetic studies, using both the candidate gene and genome-wide approach, have been undertaken to tease out the genetic basis of PE and understand its origins. Such studies have identified some promising candidate genes such as STOX1 and ACVR2A. Nevertheless, researchers face ongoing challenges of replicating these genetic associations in different populations and performing the functional validation of identified genetic variants to determine their causality in the disorder. This chapter will review the genetic approaches used in the study of PE, discuss their limitations and possible confounders, and describe current strategies.

Genetic Variants in Preeclampsia: Lessons From Studies in Latin-American Populations

“…The gene ACVR2A encodes the activin A type II receptor (ActRIIA), an essential factor for pregnancy establishment during decidualization, trophoblast invasion, and placentation. Concerning the regulation of trophoblast invasion, abnormal decidual ACVR2A expression may affect placentation and lead to PE development (Yong et al, 2018a). In this context, five ACVR2A SNPs (rs1424954, rs1014064, rs1424941, rs2161983, and rs3768687) were investigated in a northwestern Brazilian population approaching PE cases and controls.…”

Preeklampsja – choroba kobiet w ciąży

“…Wykazano wpływ genów matczynych i genów kodujących ludzki antygen płodu HLA-C, na pojawienie się preeklampsji, co sugeruje rolę zaburzeń odpornościowych organizmu w patogenezie tej choroby [27][28][29]. Do genów mających wpływ na rozwój preeklampsji zalicza się też STOX1 i ACVR2A [30]. Gen STOX1 koduje czynniki transkrypcyjne z rodziny fork-head/winged helix, posiadające silnie zachowaną w ewolucji domenę wiążącą DNA (ang.…”

“…W efekcie dochodzi do zaburzenia ekspresji białka, co z kolei ma wpływ na zaburzenie adhezji, proliferacji, migracji i inwazji trofoblastu. Zaburzenie ekspresji ACVR2A zwiększa ponadto przepuszczalność i hamuje proliferację komórek śródbłonka naczyniowego [30]. Co więcej, wiadomo, że nie tylko mutacje w genach, ale również mechanizmy epigenetyczne, takie jak modulacja ekspresji mikroRNA lub/i metylacja DNA, mogą być zaangażowane w rozwój preeklampsji [32].…”

Study of Preeclampsia in Placenta, Kidney, and Hepatic Diseases

“…The important role of mitochondrial activity changes in the adaptive response to the development of PE, due to increased OPA1 mRNA and protein expression in the placenta [90]. Potential genes such as STOX1 and ACVR2A were also identified determining their causality in PE disorders [91]. In PE, male fetal placenta is associated with much higher expression of inflammation, hypoxia, and apoptosis than female fetal placenta but reduces the expression of pro-angiogenic markers [92].…”