title: Hypoxia-inducible factor-1α gene polymorphisms in early and late onset preeclampsia in Sinhalese women.
abstract: BACKGROUND
  Early (EPE) and late (LPE) onset preeclampsia are increasingly being recognized as two distinct disorders. Placental vascular defects are more common in EPE. Hypoxia Inducible Factor 1α (HIF1α) regulates the expression of many angiogenic growth factors in the placenta. We studied the association of two polymorphisms in the HIF1α gene (rs11549465 and rs10873142) with EPE and LPE.
  
  
  METHODS
  175 nulliparous Sinhalese women with preeclampsia and 171 normotensive women matched for age, ethnicity, parity and BMI were recruited at two tertiary care hospitals in Colombo. Preeclampsia was diagnosed using international guidelines. DNA extracted from peripheral blood was genotyped using Sequenom MassARRAY.
  
  
  RESULTS
  HIF1α rs11549465 dominant model and T allele were reduced in women who developed EPE compared to controls [P = 0.002, OR (95% CI) = 0.3 (0.1-0.7)], in preeclamptic women who delivered small for gestational age babies [P = 0.02, OR (95% CI) = 0.5 (0.2-0.9)] compared to controls and in women who developed EPE compared to those who developed LPE [P = 0.006, OR (95% CI) = 0.3 (0.1-0.7)].
  
  
  CONCLUSIONS
  Our results demonstrate a protective effect of the T allele in LPE and normal pregnancy, which is relatively lacking in EPE due to low prevalence of this protective allele. HIF1α rs11549465 T allele was previously demonstrated to be associated with a higher transcriptional activity and increased angiogenesis. Inherited susceptibility to increased HIF1α expression resulting in the up-regulation of angiogenic genes may mediate a protective effect in normal pregnancy and pregnancy complicated by LPE.
authors.affiliation: School of Paediatrics and Reproductive Health, Robinson Institute, University of Adelaide, Adelaide, Australia; Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka. Electronic address: prabha.andraweera@adelaide.edu.au.
authors.forename: P H
authors.initials: PH
authors.lastname: Andraweera
authors.affiliation: School of Paediatrics and Reproductive Health, Robinson Institute, University of Adelaide, Adelaide, Australia; Women's and Children's Division, Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia.
authors.forename: G A
authors.initials: GA
authors.lastname: Dekker
authors.affiliation: School of Paediatrics and Reproductive Health, Robinson Institute, University of Adelaide, Adelaide, Australia.
authors.forename: S D
authors.initials: SD
authors.lastname: Thompson
authors.affiliation: Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
authors.forename: V H W
authors.initials: VH
authors.lastname: Dissanayake
authors.affiliation: Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
authors.forename: R W
authors.initials: RW
authors.lastname: Jayasekara
authors.affiliation: School of Paediatrics and Reproductive Health, Robinson Institute, University of Adelaide, Adelaide, Australia.
authors.forename: C T
authors.initials: CT
authors.lastname: Roberts
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D007231:Infant, Newborn; D007234:Infant, Premature; D007236:Infant, Small for Gestational Age; D008297:Male; D009389:Neovascularization, Pathologic / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D013188:Sri Lanka; D013997:Time Factors; D055815:Young Adult
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: Hypoxia inducible factor 1α; Polymorphism; Preeclampsia