Locus rs833061 of the VEGF Gene in Pregnant Women with Preeclampsia Is Associated with Newborn Weight

Abstract

We studied the associations of newborn weight with polymorphic loci of growth factor genes in pregnant women with preeclampsia (PE) and considered their regulatory potential. In the group of pregnant women with PE (n = 190), a molecular genetic study of five polymorphic loci of growth factor genes was performed: rs4444903 EGF, rs833061 VEGFA, rs2981582 FGFR2, rs6214 IGF1, rs1800469 TGFβ1. Newborn somatometry was performed using standard methods. Associations of the studied polymorphic loci with newborn weight were studied using log-linear regression analysis. It was found that the genetic risk factor for the birth of small children in pregnant women with PE is the allele C of the rs833061 polymorphism of the VEGFA gene (p perm = 0.002): women with the T/T genotype have the highest newborn weight (on average 3524 g), while women with the C/C genotype have the minimum newborn weight (on average 3415 g). It is shown that the allele C of polymorphic locus rs833061 is associated with low transcription of the VEGFA gene in the thyroid gland and a higher level of alternative splicing of the VEGFA gene transcript in skeletal muscle, increases the affinity of DNA for transcription factors BCL, Pax-5, and Znf143, and affects the interaction of DNA with more than 20 different regulatory proteins (CTCF, RAD21, ZNF263, MAX, etc.). It is revealed that polymorphism rs833061of the VEGF gene in pregnant women with PE is associated with weight of the newborn and has considerable regulatory potential.