22: Maternal, paternal and fetal single nucleotide polymorphisms in vascular endothelial growth factor family genes associate with pregnancy complications


      Gestational hypertension (GHT), preeclampsia (PE) and pregnancies complicated by small for gestational age babies (SGA) contribute to maternal and neonatal morbidity and mortality. Vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are angiogenic factors which act via Flt-1 (fms-like tyrosine kinase 1) and KDR (kinase insert domain receptor) receptors. Reduced maternal plasma VEGF and PlGF and elevated sFlt-1 are implicated in PE and SGA. We hypothesised that polymorphisms in VEGF (C2578A), PlGF (C642A), KDR (T604C) and Flt-1 (C677T) genes associate with pregnancy complications.

      Study Design

      1169 nulliparous pregnant women and their partners were recruited prospectively for the Adelaide SCOPE study. GHT, PE and SGA were classified using strict guidelines. Uncomplicated pregnancies served as controls. Peripheral blood from couples and cord blood from babies were collected. DNA extraction and genotyping were performed using the Sequenom MassARRAY system. Genotypes for caucasian GHT (n=74), PE (n=71) and SGA (n=101) were compared with controls (n=408) and analysed using ANOVA and Chi Square.


      Neonatal VEGFC2578A associate with PE (p=0.01, OR=2.3, 95%CI=1.2-4.4). Maternal and neonatal PlGFC642A associate with GHT (p=0.01, OR=1.14, 95%CI=1.2-7.9; p=0.027, OR=4.65, 95%CI=1.1-19.8). Paternal and neonatal KDRT604C associate with PE (p=0.04, OR=1.9, 95%CI=1.0-3.5; p=0.03, OR=2.2, 95%CI=1.1-4.4). Paternal and neonatal KDRT604C associate with SGA (p=0.004, OR=2.1, 95%CI=1.3-3.5; p=0.009, OR=2.2, 95% CI=1.2-3.9). Neonatal KDRT604C CC associate with 9.9 lower customised birthweight centile (p=0.039), 198g lower birthweight (p=0.013) and 61g lower placental weight (p=0.007) compared to TT. Paternal KDRT604C CC associate with 10.5 lower customised birthweight centile compared to CT (p=0.004).


      Our results suggest that maternal and importantly paternal SNPs in VEGF family genes act through the placenta to confer risk for pregnancy complications. Ongoing research will determine the role of these polymorphisms in placental function.