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OP006. A preeclampsia genome-wide linkage scan in norwegian families
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Oral Presentations / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 3 (2013) 62–66
OP005. Preeclampsia is associated with the presence of transcriptionally active placental fragments in the maternal lung Buurma Aletta, Penning Marlies, Prins Frans, Schutte Joke, Bruijn Jan Antonie, Rajakumar Augustine, Bloemenkamp Kitty, Karumanchi Ananth, Baelde Hans Introduction: Preeclampsia is associated with increased levels of the circulating anti-angiogenic factor sFlt-1 as well as with an excessive shedding of placenta-derived multinucleated syncytial aggregates into the maternal circulation. However, it remains unclear whether these aggregates are transcriptionally active in the maternal organs and can therefore contribute to the systemic manifestations of preeclampsia. Objectives: We hypothesized that in preeclampsia, syncytial knots are the primary placental site of sFlt-1 production and that increased numbers of sFlt-1-containing syncytial aggregates are retained in the maternal lungs. Methods: In this study, we measured placental sFlt-1 mRNA levels in preeclamptic- and control placentas and performed RNA in situ hybridization to localize the main placental expression site of sFlt-1 mRNA. Because the maternal lung is the first capillary bed that circulating syncytial aggregates traverse, we studied the presence and persistence of placental material in lungs of preeclamptic women and control subjects. To confirm the placental origin of suspected syncytial aggregates in these lungs, immunohistochemistry for the placenta-specific marker hCG and Y-chromosome in situ hybridization were performed. Results: Using human placental tissue, we found that syncytial knots are the principal site of expression of the antiangiogenic factor sFlt-1. In addition, in autopsy material obtained from women with preeclampsia (n = 9), we observed significantly more placenta-derived syncytial aggregates in the lungs than in control subjects (n = 26). Importantly, these placental aggregates still contained the anti-angiogenic factor sFlt-1 following their entrapment in the maternal lungs. Conclusion: The current study confirms the important role of syncytial knots in placental sFlt-1 mRNA production. Additionally, it shows a significant association between preeclampsia and larger quantities of sFlt-1 containing syncytial aggregates in maternal lungs, suggesting that the transfer of syncytial aggregates to the maternal compartment may contribute to the systemic endothelial dysfunction that characterizes preeclampsia. doi:10.1016/j.preghy.2013.04.021
OP006. A preeclampsia genome-wide linkage scan in Norwegian families Linda Tømmerdal Roten, Matthew P. Johnson, Liv Cecilie V. Thompsen, Astrid S. Gundersen, Per Solberg, Kjersti Tollaksen, Ingvill Lyslo, Christian Tappert, Maria Lisa Odland, Kristin M. Strand, Mona H. Fenstad, Finn Drabløs, Frank Skorpen, Eric K. Moses, Rigmor Austgulen, Line Bjørge
Introduction: Several maternal susceptibility loci for preeclampsia (PE) have been discovered amongst Icelandic, Australian/New Zealand, Dutch and Finnish family cohorts, implicating locus heterogeneity. Through candidate gene studies, allele-specific heterogeneity in different populations is also evident. It is therefore likely that numerous population specific PE susceptibility variants exist, differing in their effect size. Despite on-going efforts to identify susceptibility genes for PE, the causal genetic variants still remain obscure. Objectives: The aim of this study is to interrogate the genetic architecture of PE susceptibility by performing a genome-wide linkage scan in a novel familial cohort from Norway. Methods: A total of 480 DNA samples from The Norwegian PE Family Biobank were genotyped at Genomic Core Facility at NTNU. Genome-wide genotyping was performed with the Infinium HumanExome BeadChip (>240,000 markers) (Illumina, USA) that delivers focused coverage of exonic regions of the human genome. Results: A total of 137 families are represented with 222 women with a valid PE diagnosis (SBP P 140 mmHg DBP P 90 mmHg, P2 measurements at least 4 h apart with documented proteinuria at P2 occasions occurring after 20 weeks of pregnancy), 44 with self-reported PE and 72 women with a healthy pregnancy. The genotyping has just recently been completed with an average call rate of 99.96%. Data and statistical analysis is now underway using MERLIN, R and SOLAR. A description of the Norwegian PE familial cohort plus preliminary results will be presented at the Congress. Conclusion: To our knowledge this is the first SNP-based genome-wide linkage study on PE, and the first performed in a novel Norwegian PE family cohort. By using an approach focusing on functionally relevant markers we anticipate the identification of susceptibility loci that are of substantial importance for disease development. doi:10.1016/j.preghy.2013.04.022
Clinical research OP007. PLGF in combination with other commonly utilised tests and other biomarkers for predicting need for delivery for pre-eclampsia within 14 days in women presenting prior to 35 weeks’ gestation Chappell Lucy, Duckworth Suzy, Griffin Melanie, Seed Paul, Redman Christopher, Shennan Andrew Introduction: Current means of assessing women presenting with suspected pre-eclampsia using BP and proteinuria are of limited use in predicting need for imminent delivery. Objectives/Method/Design: We undertook a prospective multicentre study to determine diagnostic accuracy of PlGF <5th centile (Triage assay) and other candidate biomarkers in women presenting with suspected pre-eclampsia at 20– 35 weeks’ gestation, in determining need for delivery for pre-eclampsia within 14 days. We calculated ROC curves for predictive potential and undertook principal factor analysis to determine additional predictive ability for biomarker combinations.
Oral Presentations / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 3 (2013) 62–66
OP005. Preeclampsia is associated with the presence of transcriptionally active placental fragments in the maternal lung Buurma Aletta, Penning Marlies, Prins Frans, Schutte Joke, Bruijn Jan Antonie, Rajakumar Augustine, Bloemenkamp Kitty, Karumanchi Ananth, Baelde Hans Introduction: Preeclampsia is associated with increased levels of the circulating anti-angiogenic factor sFlt-1 as well as with an excessive shedding of placenta-derived multinucleated syncytial aggregates into the maternal circulation. However, it remains unclear whether these aggregates are transcriptionally active in the maternal organs and can therefore contribute to the systemic manifestations of preeclampsia. Objectives: We hypothesized that in preeclampsia, syncytial knots are the primary placental site of sFlt-1 production and that increased numbers of sFlt-1-containing syncytial aggregates are retained in the maternal lungs. Methods: In this study, we measured placental sFlt-1 mRNA levels in preeclamptic- and control placentas and performed RNA in situ hybridization to localize the main placental expression site of sFlt-1 mRNA. Because the maternal lung is the first capillary bed that circulating syncytial aggregates traverse, we studied the presence and persistence of placental material in lungs of preeclamptic women and control subjects. To confirm the placental origin of suspected syncytial aggregates in these lungs, immunohistochemistry for the placenta-specific marker hCG and Y-chromosome in situ hybridization were performed. Results: Using human placental tissue, we found that syncytial knots are the principal site of expression of the antiangiogenic factor sFlt-1. In addition, in autopsy material obtained from women with preeclampsia (n = 9), we observed significantly more placenta-derived syncytial aggregates in the lungs than in control subjects (n = 26). Importantly, these placental aggregates still contained the anti-angiogenic factor sFlt-1 following their entrapment in the maternal lungs. Conclusion: The current study confirms the important role of syncytial knots in placental sFlt-1 mRNA production. Additionally, it shows a significant association between preeclampsia and larger quantities of sFlt-1 containing syncytial aggregates in maternal lungs, suggesting that the transfer of syncytial aggregates to the maternal compartment may contribute to the systemic endothelial dysfunction that characterizes preeclampsia. doi:10.1016/j.preghy.2013.04.021
OP006. A preeclampsia genome-wide linkage scan in Norwegian families Linda Tømmerdal Roten, Matthew P. Johnson, Liv Cecilie V. Thompsen, Astrid S. Gundersen, Per Solberg, Kjersti Tollaksen, Ingvill Lyslo, Christian Tappert, Maria Lisa Odland, Kristin M. Strand, Mona H. Fenstad, Finn Drabløs, Frank Skorpen, Eric K. Moses, Rigmor Austgulen, Line Bjørge
Introduction: Several maternal susceptibility loci for preeclampsia (PE) have been discovered amongst Icelandic, Australian/New Zealand, Dutch and Finnish family cohorts, implicating locus heterogeneity. Through candidate gene studies, allele-specific heterogeneity in different populations is also evident. It is therefore likely that numerous population specific PE susceptibility variants exist, differing in their effect size. Despite on-going efforts to identify susceptibility genes for PE, the causal genetic variants still remain obscure. Objectives: The aim of this study is to interrogate the genetic architecture of PE susceptibility by performing a genome-wide linkage scan in a novel familial cohort from Norway. Methods: A total of 480 DNA samples from The Norwegian PE Family Biobank were genotyped at Genomic Core Facility at NTNU. Genome-wide genotyping was performed with the Infinium HumanExome BeadChip (>240,000 markers) (Illumina, USA) that delivers focused coverage of exonic regions of the human genome. Results: A total of 137 families are represented with 222 women with a valid PE diagnosis (SBP P 140 mmHg DBP P 90 mmHg, P2 measurements at least 4 h apart with documented proteinuria at P2 occasions occurring after 20 weeks of pregnancy), 44 with self-reported PE and 72 women with a healthy pregnancy. The genotyping has just recently been completed with an average call rate of 99.96%. Data and statistical analysis is now underway using MERLIN, R and SOLAR. A description of the Norwegian PE familial cohort plus preliminary results will be presented at the Congress. Conclusion: To our knowledge this is the first SNP-based genome-wide linkage study on PE, and the first performed in a novel Norwegian PE family cohort. By using an approach focusing on functionally relevant markers we anticipate the identification of susceptibility loci that are of substantial importance for disease development. doi:10.1016/j.preghy.2013.04.022
Clinical research OP007. PLGF in combination with other commonly utilised tests and other biomarkers for predicting need for delivery for pre-eclampsia within 14 days in women presenting prior to 35 weeks’ gestation Chappell Lucy, Duckworth Suzy, Griffin Melanie, Seed Paul, Redman Christopher, Shennan Andrew Introduction: Current means of assessing women presenting with suspected pre-eclampsia using BP and proteinuria are of limited use in predicting need for imminent delivery. Objectives/Method/Design: We undertook a prospective multicentre study to determine diagnostic accuracy of PlGF <5th centile (Triage assay) and other candidate biomarkers in women presenting with suspected pre-eclampsia at 20– 35 weeks’ gestation, in determining need for delivery for pre-eclampsia within 14 days. We calculated ROC curves for predictive potential and undertook principal factor analysis to determine additional predictive ability for biomarker combinations.