GENETIC DETERMINANTS OF GESTOSIS (PREECLAMPSIA): POLYMORPHISMS IN METABOLIC, IMMUNE, HEMOSTATIC, AND VASCULAR GENES AND THEIR CLINICAL RELEVANCE

Abstract

Background. Gestosis/preeclampsia is a leading pregnancy complication with marked phenotypic heterogeneity. Evidence from familial aggregation, population studies, and molecular genetics supports a substantial heritable component involving maternal, paternal, and fetal genomes.
Objective. To summarize current evidence on genetic susceptibility to preeclampsia, systematize major candidate-gene pathways (xenobiotic metabolism/oxidative stress, HLA-mediated immune tolerance, hemostasis and folate cycle, endothelial dysfunction and RAAS), and outline clinically relevant risk-stratification directions.
Materials and Methods. Narrative analytical review of clinical and molecular genetic studies, including familial studies, GWAS/meta-analyses, and candidate polymorphisms in GST genes, HLA-G, FV/FII, MTHFR, NOS3, ACE/AGT/AGTR, and PAI-1.
Results. Preeclampsia emerges from gene–environment interactions affecting maternal–placental immune adaptation, endothelial integrity, pro-/anticoagulant balance, and inflammatory–metabolic responsiveness. The most consistently replicated signals cluster around angiogenic pathways, thrombophilia, and vascular tone regulation; however, effect sizes of individual polymorphisms vary by ancestry, phenotype (early- vs late-onset), and comorbid risk factors.
Conclusion. The genetic architecture of preeclampsia is polygenic and multifactorial. Integrating clinical history with polygenic risk scores and placental dysfunction biomarkers is a promising route toward personalized prevention and surveillance in high-risk pregnancies.