The Impact of Polygenic Mutation Combinations on the Progression and Outcomes of Severe Preeclampsia

Introduction. Preeclampsia remains one of the most significant challenges in modern obstetrics, accounting for approximately 2–8% of maternal and perinatal losses. The complexity of the pathophysiological mechanisms underlying preeclampsia limits the available diagnostic and preventive measures for this pregnancy complication, leading to an increased incidence of preterm delivery. One promising area of research in preeclampsia pathophysiology is the study of genetic factors contributing to coagulation disorders, placental dysfunction, and hypoxic-ischemic injuries in neonates affected by preeclampsia. The objective of this study is to evaluate the role of combined mutations in genes related to the antioxidant system (SOD2 (C47T), CAT (-262C/T), GSTP1 (313A>G)), platelet integrins (ITGB3 (T1565C), ITGA2 (C807T)), and fibrinogen (FGB (G(-455)A)) in the development of severe preeclampsia and adverse perinatal outcomes. Materials and methods. A single-center, observational, prospective study was conducted involving 49 female patients (2018–2022), who were divided into three groups: Group A (n = 16) comprised patients with severe preeclampsia and fewer than 6 mutant alleles of the aforementioned genes; Group B (n = 18) included patients with severe preeclampsia and 6 or more mutant alleles of the aforementioned genes; Group 0 (n = 15) consisted of patients with a physiologically normal pregnancy and fewer than 6 mutant alleles of the aforementioned genes. Thromboelastography, peripheral tissue microcirculation, and the intensity of oxidative processes in the blood were assessed. Genetic testing was performed using real-time PCR. Neonatal outcomes were evaluated using the Apgar score (4–6 points indicating moderate asphyxia, 1–3 points indicating severe asphyxia). Results. In Group B, statistically significant (p < 0.05) thromboelastography changes were observed, characterized by reduced blood clot solubility, increased thrombus formation rate, and impaired oxygenation processes. A decrease in microcirculation efficiency and an intensification of oxidative stress processes were noted. Additionally, a statistically significant (p < 0.05) increase in lipid peroxidation products (malondialdehyde and diene conjugates) was recorded, accompanied by reduced antioxidant activity compared to both the control group and Group A. Discussion and conclusion. The combination of mutant variants of the studied platelet integrin genes and antioxidant genes in the presence of homozygous mutant alleles is associated with impaired oxidative processes and coagulation potential in severe preeclampsia, as well as the development of severe neonatal asphyxia.