Epistasis of hemostasis and folate cycle genes in fetal growth restriction and early-onset preeclampsia

To investigate the frequency of single nucleotide polymorphisms in genes of the hemostatic system and the folate cycle, as well as their intergenic interactions, in patients with antenatally diagnosed fetal growth restriction with and without clinical manifestations of preeclampsia. The study included 255 delivery records. The first (control) group consisted of 70 cases of normal deliveries in conditionally healthy pregnant women. The second group comprised 90 cases of deliveries complicated by fetal growth restriction without clinical signs of preeclampsia. The third group included 95 cases of deliveries with diagnosed early–onset preeclampsia and fetal growth restriction at a gestational age of 20–34 weeks. In patients from all groups, genetic polymorphisms associated with the hemostatic system and folate metabolism were determined using real-time polymerase chain reaction. Epistasis analysis was performed using the Generalized Multifactor Dimensionality Reduction (GMDR) v. 0,7 method. Predictive models of varying complexity were constructed. For the group with fetal growth restriction without clinical preeclampsia, the three-locus model. For the group with fetal growth restriction accompanied by preeclampsia, the most effective was the five–locus model. Specific high-risk genotypic profiles were identified for each form of the pathology. Distinct variants of the genetic architecture underlying isolated fetal growth restriction and fetal growth restriction associated with preeclampsia were identified. Combined analysis of polymorphisms in hemostasis- and folate cycle related genes enables early prediction and risk stratification of placental disorders.

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