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Introduction. Preeclampsia (PE) is a serious complication of pregnancy that occurs in 3-8% of pregnant women and is the leading cause of maternal and perinatal morbidity and mortality.Aim. To evaluate the role of vascular homeostasis gene polymorphism in the formation of preeclampsia.Materials and methods. The sample for this study included 250 women with preeclampsia and 209 women with normal gestation (control group). Five polymorphic loci of vascular homeostasis genes were selected for analysis: α-adducin (G460W ADD1), β2-adrenoceptor (+46G/A ADRB2), endothelin-1 (Lys198Asn EDN1) encoding the β3 G protein subunit (G/A GNB3), cytochrome 3A5 (+6986G/A CYP3A5). The molecular genetic study of all SNPs was carried out by polymerase chain reaction.Results. It was found that genetic variants determine the risk of developing preeclampsia. The allelic variant 198Lys EDN1 (84.80%) occurs in women with a clinical diagnosis of PE significantly more often than in women of the control group (79.67%) (p = 0.05; OR = 1.43; 95%CI 1.01–2.03). At the same time, among pregnant women without PE, combinations of 198Asn EDN1 x +46 A ADRB2 (23.65%) and 198Asn EDN1 x 460 ADD1 x +46 A ADRB2 (23.65%) are registered 1.6–1.7 times more often than among women with PE (14.46 and 13.65%, respectively, рperm = 0.032). Conclusion. The risk factor for the formation of preeclampsia is the 198Lys EDN1 allele (OR = 1.43), and combinations of genetic variants 198Asn EDN1 х +46 A ADRB2 (OR = 0.55) and 198Asn EDN1 х +46 A ADRB2 х 460G ADD1 (OR = 0.51) have a protective value.