Study of associations of candidate genes differentially expressed in the placenta with the development of placental insufficiency with fetal growth restriction
Background: Placental insufficiency (PI) is a key feature of pregnancies with fetal growth restriction (FGR). FGR is defined as pathological inhibition of intrauterine growth of the fetus and its inability to reach its growth potential. The aim of the study: To study the associations of single nucleotide polymorphisms of candidate genes, differentially expressed in the placenta, with the development of placental insufficiency with fetal growth retardation syndrome. Materials and methods: The study group included 273 pregnant women with placental insufficiency and growth retardation syndrome and 631 women with physiological pregnancy. All women underwent typing of ten single nucleotide polymorphisms of five genes differentially expressed in the placenta (HK2, BCL6, NDRG1, ENG, RDH13). The analysis of associations of polymorphic markers with the development of PI with FGR allows the use of logistic regression analysis in the framework of additive, dominant and recessive genetic models. Results: Allele A rs10496196 HK2 is associated with the development of placental insufficiency with FGR within the additive (OR = 1.40, 95% Сl 1.05-1.87, p = 0.024) and dominant (OR = 1.44, 95% Сl 1, 04-2.0, p = 0.03) models of the interaction of alleles. In addition, this polymorphic locus is associated with the level of transcription of 5 genes (HK2, POLE4, AC104135.2, AC104135.3, AC104135.4) in various organs and tissues (pFDR≤0.05), as well as with the level of alternative splicing of the MTHFD2 gene transcript in blood and the POLE4 gene in skin (pFDR≤0.05). Conclusion: Allele A rs10496196 HK2 is a risk factor for the development of placental insufficiency with fetal growth retardation syndrome in pregnant women in the Central Black Earth Region of Russia.