The Role of Gene–Gene Interactions in the Formation of Predisposition to Preeclampsia

Abstract—Identification of the hereditary basis of preeclampsia remains a relevant area for medical genetics. Despite numerous attempts to search for the main predetermining factors, due to the multifactorial nature of the preeclampsia no generally accepted hypotheses for the pathogenesis of this pregnancy complication exists. One of the progressive approaches to the study of complex diseases is an analysis of gene–gene interactions, which makes it possible to isolate factors that can determine a high or low risk of predisposition within the pathology from a large array of combinations. In the presented work, analysis of gene–gene interactions was used to create a model that predicts the risk of severe preeclampsia and find key combinations of genes predisposing one to the development of preeclampsia in the Russian population. For the first time the prognostic potential of combinations of the rs3774298 BCL6 and rs2071045 LEP loci in the development of a severe form of preeclampsia (OR = 2.97) was demonstrated. Additionally, it was found that the rs3774298 polymorphic variant of the BCL6 gene is located in a functionally active region of the genome located in the binding site of the transcription factor CTCF, which can function as both a transcription activator and a repressor. This emphasizes the role of cell regulatory systems in the mechanisms of the formation and course of preeclampsia.