161. PATERNAL AND FETAL SINGLE NUCLEOTIDE POLYMORPHISMS IN KDR GENE ASSOCIATE WITH PREECLAMPSIA AND INTRAUTERINE GROWTH RESTRICTION

Abstract

Introduction: Preeclampsia (PE) and intrauterine growth restriction (IUGR) together contribute to maternal and neonatal morbidity and mortality. Abnormal placental angiogenesis is implicated in these pregnancy complications. KDR is the main receptor for vascular endothelial growth factor, a potent angiogenic factor which regulates placental angiogenesis. Derangements in KDR expression are known to result in abnormal angiogenesis. We aimed to determine whether polymorphisms in KDR gene (KDR T604C and KDR C1192C) are associated with PE and IUGR. Methods: 1169 nulliparous pregnant women and their partners were recruited prospectively at the Lyell McEwin Hospital and women monitored throughout pregnancy. PE and IUGR were classified using strict guidelines. Uncomplicated pregnancies were deemed controls. Peripheral blood was collected from couples and cord blood collected at delivery. DNA extraction from buffy coats and genotyping were performed at the Australian Genome Research Facility using the Sequenom MassARRAY system. Genotypes for PE (n=63) and IUGR (n=94) were compared with controls (n=373) and analysed using ANOVA and Chi Square. Odds Ratios (OR) were calculated. Results: Paternal and neonatal KDR T604C were associated with PE (p=0.028, OR=1.9, 95%CI=1.08–3.34 and p=0.008, OR=2.5, 95%CI=1.3–4.78). Paternal and neonatal KDR T604C were associated with IUGR (p=0.005, OR=2.01, 95%CI=1.24–3.25 and p=0.01, OR=1.15, 95% CI=1.22–3.79). Neonates with KDR T604C CC genotype were 144.5g lighter than those with the TT genotype (p=0.05). Mean customised birth weight centile was 8.7 lower for fathers with KDR T604C CC genotype compared to CT (p=0.041). KDR C1192T SNP was not associated with outcome. Conclusion: Our results suggest that KDR T604C polymorphism is associated with both PE and IUGR. We are the first to demonstrate an association between paternal KDR polymorphisms and pregnancy complications. Paternal genes acting via the placenta appear to contribute to the risk of PE and IUGR. Ongoing research will determine the role of these polymorphisms in placental angiogenesis.