Assessment of genetic susceptibility to the occurrence of placenta-associated complications in pregnant women with retrochorial hematomas in the trimester I of pregnancy

Abstract

Purpose - to determine the presence of genetic determinism on the part of thrombophilia and angiogenesis candidate genes, their prognostic value in the development of preeclampsia (РЕ) in women with retrochorial hematoma (RCH).

Materials and methods. The course of pregnancy was analyzed in 137 women with the threat of miscarriage aged 20 to 47 years (the Group 1 - 60 patients with RCH, the Group 2 - 77 patients without hematoma). Additionally, polymorphisms of the thrombophilia genes, the vascular endothelial growth factor gene - A (VEGF-A-634C>G) and the nitric oxide synthase 3 gene (NOS3 -786 C>T) were studied. To assess the correlation dependencies, the water-soluble tyrosine kinase-1 (sFlt-1) / placental growth factor (PlGF) (sFlt-1/PlGF) ratio was determined using TRACE-technologe (BRAHSMS Kryptor).

Results. The average age of women in the Group 1 was 31.2±0.6 (95% CI: 30.0-32.4) years, in the Group 2 was 32.2±0.6 (95% CI: 31.0-33.3) years (p=0.243 by t-criterion). The calculation of the risk of developing PE in women of both groups established a high risk of its development in 28 (46.7%) and 23 (29.9%), respectively (p=0.044 by c²). Significant correlations in pairs were revealed: F13A1 gene polymorphism (9 G>T) - a decrease in the level of PlGF (r_s=-0.296; p=0.023) and an increase in the value of sFlt-1/PlGF at 32-33⁺⁶ weeks (rs=0.248; p=0.050); FGB-fibrinogen gene (455 G>A) - the presence of chronic arterial hypertension (CAH) in a pregnant woman (r_s=0.260, p=0.002), an increased risk of developing PE in the trimester I (r_s=0.180; p=0.038); PAI-1 gene - reduced level of sFlt-1 (r_s=-0.331; p=0.010) and sFlt-1/PlGF at 32-33⁺⁶ weeks (r_s=-0.310; p=0.015); ITGB3-β gene - the presence of CAH in a pregnant woman (r_s=0.176; p=0.040), an increase in sFlt-1/PlGF (r_s=0.221; p=0.087). There was a trend towards an increased risk of developing PE in the first trimester in carriers of the VEGF-A gene polymorphism (-634 C>G) (r_s=0.226; p=0.083). NOS3 gene polymorphism was associated with increased sFlt-1 (r_s=0.252; p=0.063) and sFlt-1/PlGF ratio at 32-33⁺⁶ weeks (r_s=0.239; p=0.079).

Conclusions. Calculation of the risk of developing PE in women with RCH found a high risk of its development. The presence of VEGF-A polymorphism (-634 C>G) leads to an increased risk of developing PE and other placenta-associated complications. The presence of the NOS3 gene polymorphism (-786 C>T) affects the level of sFlt-1, leading to its increase and a change in the level of the sFlt-1/PlGF ratio at 32-33⁺⁶ weeks, which indicates an increased risk of developing late PE. The best predictor value has a combination of studying not only clinical data and biochemical parameters, but also genetic determinism.

The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies.

No conflict of interests was declared by the authors.