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Placental DNA methylation at term reflects maternal serum levels of INHA and FN1, but not PAPPA, early in pregnancy

BACKGROUND: Early detection of pregnancies at risk of complications, such as intrauterine growth restriction (IUGR) and preeclampsia (PE), is critical for improved monitoring and preventative treatment to optimize health outcomes. We predict that levels of placental-derived proteins circulating in m...

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Autores principales: Wilson, Samantha L., Blair, John D., Hogg, Kirsten, Langlois, Sylvie, von Dadelszen, Peter, Robinson, Wendy P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676901/
https://www.ncbi.nlm.nih.gov/pubmed/26654447
http://dx.doi.org/10.1186/s12881-015-0257-z
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author Wilson, Samantha L.
Blair, John D.
Hogg, Kirsten
Langlois, Sylvie
von Dadelszen, Peter
Robinson, Wendy P.
author_facet Wilson, Samantha L.
Blair, John D.
Hogg, Kirsten
Langlois, Sylvie
von Dadelszen, Peter
Robinson, Wendy P.
author_sort Wilson, Samantha L.
collection PubMed
description BACKGROUND: Early detection of pregnancies at risk of complications, such as intrauterine growth restriction (IUGR) and preeclampsia (PE), is critical for improved monitoring and preventative treatment to optimize health outcomes. We predict that levels of placental-derived proteins circulating in maternal blood reflect placental gene expression, which is associated with placental DNA methylation (DNAm) profiles. As such, placental DNAm profiling may be useful to distinguish pregnancies at risk of developing complications and correlation between DNAm and protein levels in maternal blood may give further evidence for a protein’s use as a biomarker. However, few studies investigate all clinical parameters that may influence DNAm and/or protein expression, which can significantly affect the relationship between these measures. RESULTS: Candidate genes were chosen based on i) reported alterations of protein levels in maternal blood and ii) observed changes in placental DNAm (∆β > 0.05 and False Discovery Rate (FDR) <0.05) in pregnancies complicated by PE/IUGR. Fibronectin (FN1) enhancer DNAm and placental gene expression were inversely correlated (r = −0.88 p < 0.01). The same trend was observed between promoter DNAm and gene expression for INHBA and PAPPA, though not significant. INHBA and FN1 DNAm was associated with gestational–age corrected birth weight, while INHA levels were associated with fetal: placental weight ratio and FN1 level was associated with maternal body mass index (BMI). DNAm at the INHBA promoter in the term placenta was negatively correlated with second trimester maternal serum levels (r = −0.50 p = 0.01) and DNAm at the FN1 enhancer was negatively associated with third trimester maternal serum levels (r = −0.38, p = 0.009). However, a similar correlation was not found for PAPPA. CONCLUSIONS: These results show that establishing a correlation between altered DNAm in the term placenta and altered maternal serum levels of the corresponding protein, is affected by a number of factors. Nonetheless, the correlation between placental DNAm of INHBA/FN1 and maternal serum INHA/FN1 levels indicate that DNAm may be a useful tool to identify novel biomarkers for adverse pregnancy outcomes in some cases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0257-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-46769012015-12-13 Placental DNA methylation at term reflects maternal serum levels of INHA and FN1, but not PAPPA, early in pregnancy Wilson, Samantha L. Blair, John D. Hogg, Kirsten Langlois, Sylvie von Dadelszen, Peter Robinson, Wendy P. BMC Med Genet Research Article BACKGROUND: Early detection of pregnancies at risk of complications, such as intrauterine growth restriction (IUGR) and preeclampsia (PE), is critical for improved monitoring and preventative treatment to optimize health outcomes. We predict that levels of placental-derived proteins circulating in maternal blood reflect placental gene expression, which is associated with placental DNA methylation (DNAm) profiles. As such, placental DNAm profiling may be useful to distinguish pregnancies at risk of developing complications and correlation between DNAm and protein levels in maternal blood may give further evidence for a protein’s use as a biomarker. However, few studies investigate all clinical parameters that may influence DNAm and/or protein expression, which can significantly affect the relationship between these measures. RESULTS: Candidate genes were chosen based on i) reported alterations of protein levels in maternal blood and ii) observed changes in placental DNAm (∆β > 0.05 and False Discovery Rate (FDR) <0.05) in pregnancies complicated by PE/IUGR. Fibronectin (FN1) enhancer DNAm and placental gene expression were inversely correlated (r = −0.88 p < 0.01). The same trend was observed between promoter DNAm and gene expression for INHBA and PAPPA, though not significant. INHBA and FN1 DNAm was associated with gestational–age corrected birth weight, while INHA levels were associated with fetal: placental weight ratio and FN1 level was associated with maternal body mass index (BMI). DNAm at the INHBA promoter in the term placenta was negatively correlated with second trimester maternal serum levels (r = −0.50 p = 0.01) and DNAm at the FN1 enhancer was negatively associated with third trimester maternal serum levels (r = −0.38, p = 0.009). However, a similar correlation was not found for PAPPA. CONCLUSIONS: These results show that establishing a correlation between altered DNAm in the term placenta and altered maternal serum levels of the corresponding protein, is affected by a number of factors. Nonetheless, the correlation between placental DNAm of INHBA/FN1 and maternal serum INHA/FN1 levels indicate that DNAm may be a useful tool to identify novel biomarkers for adverse pregnancy outcomes in some cases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0257-z) contains supplementary material, which is available to authorized users. BioMed Central 2015-12-11 /pmc/articles/PMC4676901/ /pubmed/26654447 http://dx.doi.org/10.1186/s12881-015-0257-z Text en © Wilson et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Wilson, Samantha L.
Blair, John D.
Hogg, Kirsten
Langlois, Sylvie
von Dadelszen, Peter
Robinson, Wendy P.
Placental DNA methylation at term reflects maternal serum levels of INHA and FN1, but not PAPPA, early in pregnancy
title Placental DNA methylation at term reflects maternal serum levels of INHA and FN1, but not PAPPA, early in pregnancy
title_full Placental DNA methylation at term reflects maternal serum levels of INHA and FN1, but not PAPPA, early in pregnancy
title_fullStr Placental DNA methylation at term reflects maternal serum levels of INHA and FN1, but not PAPPA, early in pregnancy
title_full_unstemmed Placental DNA methylation at term reflects maternal serum levels of INHA and FN1, but not PAPPA, early in pregnancy
title_short Placental DNA methylation at term reflects maternal serum levels of INHA and FN1, but not PAPPA, early in pregnancy
title_sort placental dna methylation at term reflects maternal serum levels of inha and fn1, but not pappa, early in pregnancy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676901/
https://www.ncbi.nlm.nih.gov/pubmed/26654447
http://dx.doi.org/10.1186/s12881-015-0257-z
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