Pathogenesis of Preeclampsia: The Genetic Component

Abstract

Preeclampsia (PE) is one of the main causes of maternal and fetal morbidity and mortality in the world, causing nearly 40% of births delivered before 35 weeks of gestation. PE begins with inadequate trophoblast invasion early in pregnancy, which produces an increase in oxidative stress contributing to the development of systemic endothelial dysfunction in the later phases of the disease, leading to the characteristic clinical manifestation of PE. Numerous methods have been used to predict the onset of PE with different degrees of efficiency. These methods have used fetal/placental and maternal markers in different stages of pregnancy. From an epidemiological point of view, many studies have shown that PE is a disease with a strong familiar predisposition, which also varies according to geographical, socioeconomic, and racial features, and this information can be used in the prediction process. Large amounts of research have shown a genetic association with a multifactorial polygenic inheritance in the development of this disease. Many biological candidate genes and polymorphisms have been examined in their relation with PE. We will discuss the most important of them, grouped by the different pathogenic mechanisms involved in PE.

Metabolic Pathways Involved in 2-Methoxyestradiol Synthesis and Their Role in Preeclampsia

“…49 A review of these alternative pathways has been published elsewhere. 61 In 2010, Shenoy et al hypothesized that there is a connection between angiogenic and metabolic pathways in the development of PE. They proposed that high levels of homocysteine could mediate inhibition of COMT, due to an increase in SAH production, a potent COMT inhibitor.…”

Role of hsa-miR-325 in the etiopathology of preeclampsia

“…Changes in hsa-miR-325 expression, in the case of pregnancy-related hypertensive disorders, may affect the oxidative stress pathways and heat-shock protein production. These factors have a strong correlation with the developement of PE (16)(17)(18). Our findings therefore may provide novel targets for further investigation of the pathogenesis of PE and these differential miRNAs may be potential markers for the diagnosis of PE.…”

Papel protetor do alelo G do polimorfismo no gene Interleucina 10 (-1082G/A) contra o desenvolvimento de pré-eclâmpsia

“…Dois componentes principais poderiam ser causadores da resposta inflamatória exacerbada: o estímulo excessivo ou a resposta materna exagerada à presença da placenta 7 . Do ponto de vista epidemiológico, muitos estudos têm indicado que a PE é uma doença associada a forte predisposição familiar, e que varia também de acordo com características geográficas, socioeconômicas e raciais da amostra analisada 8,9 . Somado a isso, foram descritos loci de suscetibilidade ao desenvolvimento da PE em diferentes populações.…”

“…Embora o genótipo paterno pareça exercer influência no aparecimento da PE, a maioria dos estudos genéticos baseia-se apenas no genótipo materno e para tal, a estratégia de genes candidatos tem sido muito empregada. Nesse sentido, genes envolvidos com a homeostase materna e sistema cardiovascular ou relacionados à regulação da resposta inflamatória materna têm sido estudados 9,13,14 . Assim, torna-se importante investigar polimorfismos em genes de citocinas que poderão ser úteis como marcadores moleculares de suscetibilidade/resistência ao desenvolvimento da PE.…”