The role of genetics in pre-eclampsia and potential pharmacogenomic interventions

Abstract

The pregnancy-specific condition pre-eclampsia not only affects the health of mother and baby during pregnancy but also has long-term consequences, increasing the chances of cardiovascular disease in later life. It is accepted that pre-eclampsia has a placental origin, but the pathogenic mechanisms leading to the systemic endothelial dysfunction characteristic of the disorder remain to be determined. In this review we discuss some key factors regarded as important in the development of pre-eclampsia, including immune maladaptation, inadequate placentation, oxidative stress, and thrombosis. Genetic factors influence all of these proposed pathophysiological mechanisms. The inherited nature of pre-eclampsia has been known for many years, and extensive genetic studies have been undertaken in this area. Genetic research offers an attractive strategy for studying the pathogenesis of pre-eclampsia as it avoids the ethical and practical difficulties of conducting basic science research during the preclinical phase of pre-eclampsia when the underlying pathological changes occur. Although pharmacogenomic studies have not yet been conducted in pre-eclampsia, a number of studies investigating treatment for essential hypertension are of relevance to therapies used in pre-eclampsia. The pharmacogenomics of antiplatelet agents, alpha and beta blockers, calcium channel blockers, and magnesium sulfate are discussed in relation to the treatment and prevention of pre-eclampsia. Pharmacogenomics offers the prospect of individualized patient treatment, ensuring swift introduction of optimal treatment whilst minimizing the use of inappropriate or ineffective drugs, thereby reducing the risk of harmful effects to both mother and baby.

Association of Angiotensinogen Gene Polymorphisms and Angiogenic Factors with Preeclampsia in Chinese Women

“…It has been suggested that genetic factors such as gene polymorphisms of the RAS may play an important role in the regulation of blood pressure in PE [21,22,23]. We revealed that pregnant women carrying the TT genotype of the AGT gene are prone to early onset of severe PE, and serum VEGF, PlGF, and sFlt-1 together contribute to the pathogenesis of PE.…”

Evaluation of Response to Antihypertensive’s in Preeclampsia and Gestational Hypertension Cases With Different Ace Gene Insertion/Deletion Genotypes

“…Such a strategy is likely to reduce the risk of harmful side effects to both mother and baby in clinical conditions such as PE and GH [16].…”

Pharmacogenetics and Individualizing Drug Treatment During Pregnancy

“…Patients with G498A polymorphism in the eNOS gene have a better blood pressure response to atenolol. If confirmed in larger studies, it is possible that the presence of eNOS polymorphisms could help inform atenolol antihypertensive therapy [38]. …”

“…The importance of both maternal and fetal genotype in this disorder is apparent [90]. The endothelial isoform of nitric oxide synthase may be important in the manifestations and the treatment of preeclampsia [38]. Smoking cessation is an important goal of prenatal care.…”