title: Single-nucleotide polymorphisms in the KDR gene in pregnancies complicated by gestational hypertensive disorders and small-for-gestational-age infants.
abstract: BACKGROUND
  Pregnancies complicated by preeclampsia and small-for-gestational-age (SGA) infants share placental vascular abnormalities and both disorders confer increased risk of later life coronary artery disease. Kinase insert domain receptor (KDR) is the main receptor for vascular endothelial growth factor A, a potent angiogenic factor which regulates the development of the placental vasculature. Two polymorphisms in KDR (-604T/C and Val297Ile) are known to be associated with coronary artery disease. We investigated the association of these polymorphisms with preeclampsia, gestational hypertension, and SGA infants.
  
  
  METHODS
  Nulliparous pregnant women, their partners, and infants were recruited to a prospective cohort study (n = 1169). Doppler ultrasound of the uterine and umbilical arteries was performed at 20 weeks of gestation. Preeclampsia, gestational hypertension, and SGA were defined according to international guidelines. DNA extracted from peripheral venous or cord blood was genotyped using the Sequenom MassARRAY system. Multivariable logistic regression was used to compare the odds for the pregnancy complications between the genotype groups adjusting for potential confounders.
  
  
  RESULTS
  Among 937 Caucasian pregnancies, 427 (45.6%) were uncomplicated, 75 (8.0%) developed preeclampsia, 102 (10.9%) developed gestational hypertension, and 72 (7.7%) had SGA infants in the absence of maternal hypertensive disease. Paternal and neonatal KDR-604T/C was associated with preeclampsia (adjusted odds ratio [aOR] 1.6, 95% confidence interval [CI] 1.0-3.0 and aOR 2.2, 95% CI 1.0-4.4), SGA (aOR 1.9, 95% CI 1.1-3.3 and aOR 2.2, 95% CI 1.2-3.9), and SGA with abnormal Doppler (aOR 2.7, 95% CI 1.2-5.9 and aOR 3.2, 95% CI 1.2-5.9).
  
  
  CONCLUSIONS
  Paternal and neonatal carriage of the KDR-604T/C polymorphism is associated with the risk of preeclampsia and SGA infants.
authors.affiliation: Discipline of Obstetrics and Gynaecology, Robinson Institute, University of Adelaide, Australia.
authors.forename: Prabha H
authors.initials: PH
authors.lastname: Andraweera
authors.forename: Gustaaf A
authors.initials: GA
authors.lastname: Dekker
authors.forename: Steven D
authors.initials: SD
authors.lastname: Thompson
authors.forename: Claire T
authors.initials: CT
authors.lastname: Roberts
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004247:DNA / Q000097:blood; D005220:Fathers; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005838:Genotype; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000235:genetics*; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011225:Pre-Eclampsia / Q000235:genetics; D011247:Pregnancy; D011446:Prospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004247:DNA; D040301:Vascular Endothelial Growth Factor Receptor-2