Hypoxia-inducible factor-1α gene polymorphisms in early and late onset preeclampsia in Sinhalese women

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...

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Published in:Placenta (Eastbourne) Vol. 35; no. 7; pp. 491 - 495
Main Authors: Andraweera, P.H., Dekker, G.A., Thompson, S.D., Dissanayake, V.H.W., Jayasekara, R.W., Roberts, C.T.
Format: Journal Article
Language:English
Published: Kidlington Elsevier Ltd 01.07.2014
Elsevier
Subjects:
Adult
Biological and medical sciences
Case-Control Studies
Embryology: invertebrates and vertebrates. Teratology
Female
Fundamental and applied biological sciences. Psychology
Gene Frequency
Genetic Predisposition to Disease
Gestational Age
Humans
Hypoxia inducible factor 1α
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
Infant, Newborn
Infant, Premature
Infant, Small for Gestational Age
Internal Medicine
Male
Neovascularization, Pathologic - genetics
Neovascularization, Physiologic - genetics
Obstetrics and Gynecology
Polymorphism
Polymorphism, Single Nucleotide
Pre-Eclampsia - etiology
Pre-Eclampsia - genetics
Pre-Eclampsia - pathology
Preeclampsia
Pregnancy
Sri Lanka
Time Factors
Young Adult
Sri Lanka
Hypoxia inducible factor 1α
Preeclampsia
Polymorphism
Human
Oxygen
Vertebrata
Late
Mammalia
Pregnancy disorders
Female
Hypoxia
Early
Pregnancy toxemia
ISSN:0143-4004, 1532-3102, 1532-3102
Online Access:Get full text
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Summary: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. 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. 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)]. 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. •Early and late onset preeclampsia are now recognized as two distinct disorders.•HIF1-α regulates many vital molecular pathways during early placentation.•HIF1α rs11549465 was investigated in women with early and late onset preeclampsia.•The T allele is protective in normal pregnancies and in late onset preeclampsia.
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ISSN:0143-4004
1532-3102
1532-3102
DOI:10.1016/j.placenta.2014.04.008