Characteristics of inter-locus interactions in the development of isolated and combined complications of pregnancy
Background: Pregnancy complications have a high prevalence and important medical and social implications. Genetic factors are involved in their development. The aim of the study:To study the characteristics of interlocus interactions in the formation of isolated and combined pregnancy complications. Materials and methods: The sample for the study consisted of 786 pregnant women, including 462 women were with various pregnancy complications (isolated preeclampsia (PE) (n=190); 2) isolated fetal growth retardation (FGR) (n=196); 3) a combination of PE and FGR (n=76)) and 324 women with a physiological course of pregnancy. Genotyping was performed for 13 polymorphic loci of growth factor genes and their receptors (rs4444903 EGF, rs833061 VEGFA, rs2981582 FGFR2, rs6214 IGF1, rs1800469 TGFß1), estrogen and progesterone receptor genes (rs2234693 ESR1, rs9340799 ESR1, rs3798577 ESR1, rs484389 PGR, rs1042838 PGR) and hereditary thrombophilia genes (rs1126643 ITGA2, rs5918 ITGB3 and rs5985 F13A1). The interaction of polymorphic loci associated with the studied pregnancy complications, visualization and determination of the nature (synergism, independent effect, antagonism) and strength (proportion of contribution to the entropy of the trait) of these interactions were studied using MB-MDR and MDR methods. Results: The risk of developing isolated FGR is determined by three models of interlocus interactions of 5 polymorphisms: rs4444903 EGF, rs6214 IGF1, rs2234693 ESR1, rs484389 PGR and rs5985 F13A1 with the most pronounced effects of the polymorphic locus rs6214 IGF1. Susceptibility to isolated PE is determined by the interlocus interactions of five loci: rs4444903 EGF, rs833061 VEGFA, rs2981582 FGFR2, rs2234693 ESR1, rs9340799 ESR1, in which the two-locus interaction rs9340799 ESR1xrs2234693 ESR1 plays a key role (it is part of all 3 models). The formation of a combination of FGR and PE is associated with two models of intergenic interactions of 4 polymorphisms: rs2234693 ESR1, rs9340799 ESR1, rs484389 PGR, rs5918 ITGB3. Three high-risk genotype combinations of genotypes showed the highest level of statistical significance of associations (p<0.005) with pregnancy complications: TT-rs2234693 ESR1xGA-rs6214 IGF1 – isolated FGR (β = 1.86, p=0.003); AA-rs9340799 ESR1xTT-rs2234693 ESR1 – isolated PE (β = 2.45, p=0.0009) and the combination of PE and FGR (β = 2.38, p=0.002). Conclusion: The risk of pregnancy complications is largely determined by the genetic combinatorics of the three polymorphic loci rs2234693 ESR1, rs9340799 ESR1, rs6214 IGF1
Golovchenko OV. Features of interlocus interactions in the formation of isolated and
combined pregnancy complications. Research Results in Biomedicine. 2024;10(4):532-552. Russian.
DOI: 10.18413/2658-6533-2024-10-4-0-4
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