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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| Veröffentlicht in: | Placenta (Eastbourne) Jg. 35; H. 7; S. 491 - 495 |
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| Abstract | 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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| AbstractList | 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. Abstract Introduction 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)]. Conclusion 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 (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.INTRODUCTIONEarly (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.METHODS175 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)].RESULTSHIF1α 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.CONCLUSIONOur 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 (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. |
| Author | Roberts, C.T. Thompson, S.D. Dissanayake, V.H.W. Jayasekara, R.W. Dekker, G.A. Andraweera, P.H. |
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| Cites_doi | 10.1515/jpm.2011.098 10.1053/siny.2000.0023 10.1016/j.ajog.2005.07.035 10.1093/humupd/dmp046 10.1016/S0002-9378(98)70160-7 10.1093/carcin/bgg132 10.3109/14767058.2012.743520 10.1186/1471-2350-10-79 10.1016/S0143-4004(98)90016-9 10.1016/j.ajog.2013.08.019 10.1111/j.1471-0528.2004.00128.x 10.1093/cvr/cvq045 10.3109/10641950903572282 10.1016/j.placenta.2012.02.013 10.1016/j.placenta.2008.11.021 10.1016/j.ahj.2007.07.042 10.1128/MCB.16.9.4604 10.1186/1756-0500-4-68 10.1093/humupd/dms011 10.1002/uog.5184 10.1186/1471-2350-9-96 10.1097/OGX.0b013e3182331028 |
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| Keywords | Hypoxia inducible factor 1α Preeclampsia Polymorphism Human Oxygen Vertebrata Late Mammalia Pregnancy disorders Female Hypoxia Early Pregnancy toxemia |
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| Snippet | Early (EPE) and late (LPE) onset preeclampsia are increasingly being recognized as two distinct disorders. Placental vascular defects are more common in EPE.... Abstract Introduction Early (EPE) and late (LPE) onset preeclampsia are increasingly being recognized as two distinct disorders. Placental vascular defects are... |
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| SubjectTerms | 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 |
| Title | Hypoxia-inducible factor-1α gene polymorphisms in early and late onset preeclampsia in Sinhalese women |
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