- Email: [email protected]
[83-OR]
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 5 (2015) 2–52
Disclosures: S. Hart: None. L. Kenny: Shareholder Metabolomic Diagnostics. J. Myers: None. P. Baker: Shareholder Metabolomic Diagnostics.
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Assay. Mean methylation levels at each CpG site were compared using an appropriate t-test. Results: One of the two CpG sites at the TSS showed significant methylation differences in PE versus NL controls at the time of D (0.53 v. 0.47; absolute difference of 6%; p < 0.018) and at NL-D compared with NL-PP (p < 0.001) but not PE-D versus PE-PP. Conclusions: Our results suggest that the changes in NCR1 expression and ultimately NK functionality that are associated with NL pregnancy yet altered in PE may be controlled by epigenetic mechanisms. Disclosures: W.M. White: None. K. Borowski: None. B. Brost: None. N. Davies: None. C. Rose: None. Z. Sun: None. T. Weissgerber: None. V.D. Garovic: None. doi:10.1016/j.preghy.2014.10.087
[84-OR] Differential DNA methylation in placental and maternal angiogenic genes is not altered in preeclampsia Cindy M. Anderson a, Jody L. Ralph b, Joyce E. Ohm b (a The Ohio State University, Columbus, OH, USA, b University of North Dakota, Grand Forks, ND, USA) doi:10.1016/j.preghy.2014.10.086
[83-OR] Altered methylation in natural cytotoxicity triggering Receptor 1 (NCR1/NKp-46) gene associated with preeclampsia at delivery Wendy M. White, Kristi Borowski, Brian Brost, Norman Davies, Carl Rose, Zhifu Sun, Tracey Weissgerber, Vesna D. Garovic (Mayo Clinic, Rochester, MN, USA) Objectives: Natural killer (NK) cells play an important role in the establishment/maintenance of normal pregnancy (NL), as well as in preeclampsia (PE). NK cells make up 5–10% of peripheral leukocytes, but comprise >70% at the uteroplacental interface. They regulate trophoblast invasion and alter the T helper 1/2 cytokine balance in NL and PE. Natural cytotoxicity receptors (NCR) are unique to the NK cell surface and lead to direct cytotoxicity as well as indirect inflammatory pathways via secreted cytokines and angiogenic factors. Acute PE has been associated with decreased expression of NCR1/NKp46 compared with NL. DNA methylation in CpGs at transcription start sites (TSS) can be inversely correlated with gene transcription. We characterized methylation patterns in the NCR1 gene in NL and PE. Methods: The methylation profile of 2 CpG sites in the NCR1 gene was analyzed in leukocyte DNA in a discovery cross-sectional cohort of 14 NL + 14 PE at delivery (D) and in a longitudinal replication cohort of 17NL + 6 PE (D v. postpartum (PP)). Genomic DNA was derived from buffy coat, bisulfite modified, then run on an Illumina Methylation
Objectives: Preeclampsia is a pregnancy-associated complex condition associated with inflammation, oxidative stress and angiogenic imbalance. Stress sensitive transcription factors nuclear factor-erythroid 2-like 1 (Nrf1) and nuclear factor-erythroid 2-like 2 (Nrf2) are involved in regulation of angiogenic, inflammatory and oxidative stress pathways. Recent evidence suggests a link between Nrf2 and angiogenic factor balance in preeclampsia though the degree to which maternal and placental DNA methylation contributes to disruption of Nrf pathways among women with preeclampsia is unknown. Our central hypothesis is that distinct patterns of DNA methylation in Nrf pathway and angiogenic genes contribute to altered angiogenic balance in preeclampsia. Methods: Prospectively, we collected blood in each of three trimesters of pregnancy, maternal white blood cells in the first trimester of pregnancy and placental tissue at delivery from nulliparous women. We analyzed DNA methylation at individual CpG dinucleotides (Illumina Infinium) in Nrf and angiogenic (VEGFA, VEGFB, VEGC, FLT1, KDR, NRF1, PlGF) genes in maternal peripheral blood cells and placenta and circulating angiogenic factors (Millipore Bioplex) from women who developed preeclampsia and normotensive controls (n = 6/group). Differences in average methylation beta scores (change in beta score >0.2 indicated significant gain of methylation; > 0.2 indicated significant loss of methylation) determined significant differences between groups. Results: DNA methylation patterns in Nrf and angiogenic genes in maternal white blood cells and placenta were not significantly different in cases/controls. Among women with preeclampsia, PlGF was significantly lower across pregnancy and sFLT1 was significantly higher in the third trimester among women with preeclampsia.
Disclosures: S. Hart: None. L. Kenny: Shareholder Metabolomic Diagnostics. J. Myers: None. P. Baker: Shareholder Metabolomic Diagnostics.
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Assay. Mean methylation levels at each CpG site were compared using an appropriate t-test. Results: One of the two CpG sites at the TSS showed significant methylation differences in PE versus NL controls at the time of D (0.53 v. 0.47; absolute difference of 6%; p < 0.018) and at NL-D compared with NL-PP (p < 0.001) but not PE-D versus PE-PP. Conclusions: Our results suggest that the changes in NCR1 expression and ultimately NK functionality that are associated with NL pregnancy yet altered in PE may be controlled by epigenetic mechanisms. Disclosures: W.M. White: None. K. Borowski: None. B. Brost: None. N. Davies: None. C. Rose: None. Z. Sun: None. T. Weissgerber: None. V.D. Garovic: None. doi:10.1016/j.preghy.2014.10.087
[84-OR] Differential DNA methylation in placental and maternal angiogenic genes is not altered in preeclampsia Cindy M. Anderson a, Jody L. Ralph b, Joyce E. Ohm b (a The Ohio State University, Columbus, OH, USA, b University of North Dakota, Grand Forks, ND, USA) doi:10.1016/j.preghy.2014.10.086
[83-OR] Altered methylation in natural cytotoxicity triggering Receptor 1 (NCR1/NKp-46) gene associated with preeclampsia at delivery Wendy M. White, Kristi Borowski, Brian Brost, Norman Davies, Carl Rose, Zhifu Sun, Tracey Weissgerber, Vesna D. Garovic (Mayo Clinic, Rochester, MN, USA) Objectives: Natural killer (NK) cells play an important role in the establishment/maintenance of normal pregnancy (NL), as well as in preeclampsia (PE). NK cells make up 5–10% of peripheral leukocytes, but comprise >70% at the uteroplacental interface. They regulate trophoblast invasion and alter the T helper 1/2 cytokine balance in NL and PE. Natural cytotoxicity receptors (NCR) are unique to the NK cell surface and lead to direct cytotoxicity as well as indirect inflammatory pathways via secreted cytokines and angiogenic factors. Acute PE has been associated with decreased expression of NCR1/NKp46 compared with NL. DNA methylation in CpGs at transcription start sites (TSS) can be inversely correlated with gene transcription. We characterized methylation patterns in the NCR1 gene in NL and PE. Methods: The methylation profile of 2 CpG sites in the NCR1 gene was analyzed in leukocyte DNA in a discovery cross-sectional cohort of 14 NL + 14 PE at delivery (D) and in a longitudinal replication cohort of 17NL + 6 PE (D v. postpartum (PP)). Genomic DNA was derived from buffy coat, bisulfite modified, then run on an Illumina Methylation
Objectives: Preeclampsia is a pregnancy-associated complex condition associated with inflammation, oxidative stress and angiogenic imbalance. Stress sensitive transcription factors nuclear factor-erythroid 2-like 1 (Nrf1) and nuclear factor-erythroid 2-like 2 (Nrf2) are involved in regulation of angiogenic, inflammatory and oxidative stress pathways. Recent evidence suggests a link between Nrf2 and angiogenic factor balance in preeclampsia though the degree to which maternal and placental DNA methylation contributes to disruption of Nrf pathways among women with preeclampsia is unknown. Our central hypothesis is that distinct patterns of DNA methylation in Nrf pathway and angiogenic genes contribute to altered angiogenic balance in preeclampsia. Methods: Prospectively, we collected blood in each of three trimesters of pregnancy, maternal white blood cells in the first trimester of pregnancy and placental tissue at delivery from nulliparous women. We analyzed DNA methylation at individual CpG dinucleotides (Illumina Infinium) in Nrf and angiogenic (VEGFA, VEGFB, VEGC, FLT1, KDR, NRF1, PlGF) genes in maternal peripheral blood cells and placenta and circulating angiogenic factors (Millipore Bioplex) from women who developed preeclampsia and normotensive controls (n = 6/group). Differences in average methylation beta scores (change in beta score >0.2 indicated significant gain of methylation; > 0.2 indicated significant loss of methylation) determined significant differences between groups. Results: DNA methylation patterns in Nrf and angiogenic genes in maternal white blood cells and placenta were not significantly different in cases/controls. Among women with preeclampsia, PlGF was significantly lower across pregnancy and sFLT1 was significantly higher in the third trimester among women with preeclampsia.