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Single-Nucleotide Polymorphisms in the KDR Gene in Pregnancies Complicated by Gestational Hypertensive Disorders and Small-for-Gestational-Age Infants

Authors
  • Andraweera, Prabha H.1, 2
  • Dekker, Gustaaf A.1, 3
  • Thompson, Steven D.1
  • Roberts, Claire T.1
  • 1 University of Adelaide, Australia , (Australia)
  • 2 University of Colombo, Sri Lanka , (Sri Lanka)
  • 3 Lyell McEwin Hospital, Elizabeth Vale, South Australia , (Australia)
Type
Published Article
Journal
Reproductive Sciences
Publisher
SAGE Publications
Publication Date
May 01, 2012
Volume
19
Issue
5
Pages
547–554
Identifiers
DOI: 10.1177/1933719111428520
Source
Springer Nature
Keywords
License
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Abstract

IntroductionPregnancies 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.MethodNulliparous 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.ResultsAmong 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).ConclusionPaternal and neonatal carriage of the KDR-604T/C polymorphism is associated with the risk of preeclampsia and SGA infants.

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