INTRODUCTION
Fetal growth retardation has common molecular mechanisms of pathogenesis with another complication of pregnancy — preeclampsia, which determines the relevance of their joint study in the context of the search for new predictors, especially genetic markers, which are simultaneously involved in both the formation of PE and FGR.
OBJECTIVE
To evaluate the association of polymorphism of GWAS-significant candidate genes of hypertension with the development of PE in pregnant women with FGR.
MATERIAL AND METHODS
The study sample included 87 women with FGR in combination with PE, the control group included 107 patients with FGR. Four polymorphic variants were genotyped: rs1173771 AC026703.1, rs9327643 PLCE1, rs805303 BAG6, rs4387287 STN1. Using logistic regression analysis, the associative relationship of the above polymorphisms with the development of PE in pregnant women with FGR was studied. Regulatory potential was assessed for polymorphic loci associated with PE in women with FGR according to materials from modern genetic databases on functional genomics (HaploReg, GTExportal, PolyPhen-2).
RESULTS AND DISCUSSION
The A allele of the polymorphic marker rs805303 BAG6 is associated with a reduced risk of PE in pregnant women with FGR (according to allelic (OR = 0.55; p=0.006), dominant (OR = 0.33; p=0.0004) and additive (OR = 0.53; p=0.006) genetic models). rs805303 BAG6 polymorphism is localized in the region of histone labels H3K27ac and H3K9ac, marking active enhancers and promoters in the culture of mesenchymal and immune cells, brain, fetal adrenal glands and etc. and the region of regulatory DNA motifs to the transcription factor CACD. The polymorphic variant rs1046089 of the PRRC2A gene, which is strongly linked to rs805303 BAG6, leads to the replacement of the amino acid arginine with histidine (Arg1740His), for which the predictor class «PROBABLY DAMAGING» is defined.
CONCLUSIONS
Polymorphic variant rs805303 of the BAG6 gene is associated with the risk of developing PE in pregnant women with FGR.
