Genetic markers of the risk of fetal growth retardation in pregnant women with preeclampsia

Abstract

Introduction. Preeclampsia (PE) and fetal growth retardation (FGR), the main mechanism of which is the pathology of the placenta, directly affect the structure of both maternal and perinatal morbidity and mortality, which determines the medical and social significance of the study of PE and FGR, especially genetic predictors of the development of these complications of gestation.Objective. To study the involvement of GWAS polymorphism of significant arterial hypertension candidate genes in the formation of FGR in pregnant women with PE.Materials and methods. The samples for the study included 83 pregnant women with PE in combination with FGR and 369 women with isolated PE who were included in the control group. All women underwent a molecular genetic study of four polymorphisms: rs932764 PLCE1, rs167479 RGL3, rs633185 ARHGAP42, rs7302981 CERS5, and studied their relationship with the development of FGR in pregnant women with PE. The functional effects of polymorphic markers, which showed significant associations with the formation of FGR in pregnant women with PE, were examined using international bioinformatic projects on functional genomics (HaploReg, GTExportal, PolyPhen-2).Results and discussion. The AA genotype of the rs9327643 locus of the PLCE1 gene significantly reduces the risk of FGR formation in pregnant women with PE according to the recessive model (OR = 0.37; p = 0.01; pperm = 0.01). The rs932764 polymorphic variant of the PLCE1 gene is located in the region of regulatory DNA motifs for 2 Hdx and Zic transcription factors, localized in the region of histone protein encoding H3K4me1 enhancers in the brain and associated with the expression of the HDAC1P1 gene in male gonad tissues.Conclusions. The polymorphic locus rs9327643 of the PLCE1 gene is associated with the risk of developing FGR in pregnant women with PE.