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Genome-scale hypomethylation in the cord blood DNAs associated with early onset preeclampsia

BACKGROUND: Preeclampsia is one of the leading causes of fetal and maternal morbidity and mortality worldwide. Preterm babies of mothers with early onset preeclampsia (EOPE) are at higher risks for various diseases later on in life, including cardiovascular diseases. We hypothesized that genome-wide...

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Autores principales: Ching, Travers, Ha, James, Song, Min-Ae, Tiirikainen, Maarit, Molnar, Janos, Berry, Marla J, Towner, Dena, Garmire, Lana X
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371797/
https://www.ncbi.nlm.nih.gov/pubmed/25806090
http://dx.doi.org/10.1186/s13148-015-0052-x
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author Ching, Travers
Ha, James
Song, Min-Ae
Tiirikainen, Maarit
Molnar, Janos
Berry, Marla J
Towner, Dena
Garmire, Lana X
author_facet Ching, Travers
Ha, James
Song, Min-Ae
Tiirikainen, Maarit
Molnar, Janos
Berry, Marla J
Towner, Dena
Garmire, Lana X
author_sort Ching, Travers
collection PubMed
description BACKGROUND: Preeclampsia is one of the leading causes of fetal and maternal morbidity and mortality worldwide. Preterm babies of mothers with early onset preeclampsia (EOPE) are at higher risks for various diseases later on in life, including cardiovascular diseases. We hypothesized that genome-wide epigenetic alterations occur in cord blood DNAs in association with EOPE and conducted a case control study to compare the genome-scale methylome differences in cord blood DNAs between 12 EOPE-associated and 8 normal births. RESULTS: Bioinformatics analysis of methylation data from the Infinium HumanMethylation450 BeadChip shows a genome-scale hypomethylation pattern in EOPE, with 51,486 hypomethylated CpG sites and 12,563 hypermethylated sites (adjusted P <0.05). A similar trend also exists in the proximal promoters (TSS200) associated with protein-coding genes. Using summary statistics on the CpG sites in TSS200 regions, promoters of 643 and 389 genes are hypomethylated and hypermethylated, respectively. Promoter-based differential methylation (DM) analysis reveals that genes in the farnesoid X receptor and liver X receptor (FXR/LXR) pathway are enriched, indicating dysfunction of lipid metabolism in cord blood cells. Additional biological functional alterations involve inflammation, cell growth, and hematological system development. A two-way ANOVA analysis among coupled cord blood and amniotic membrane samples shows that a group of genes involved in inflammation, lipid metabolism, and proliferation are persistently differentially methylated in both tissues, including IL12B, FAS, PIK31, and IGF1. CONCLUSIONS: These findings provide, for the first time, evidence of prominent genome-scale DNA methylation modifications in cord blood DNAs associated with EOPE. They may suggest a connection between inflammation and lipid dysregulation in EOPE-associated newborns and a higher risk of cardiovascular diseases later in adulthood. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-015-0052-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-43717972015-03-25 Genome-scale hypomethylation in the cord blood DNAs associated with early onset preeclampsia Ching, Travers Ha, James Song, Min-Ae Tiirikainen, Maarit Molnar, Janos Berry, Marla J Towner, Dena Garmire, Lana X Clin Epigenetics Research BACKGROUND: Preeclampsia is one of the leading causes of fetal and maternal morbidity and mortality worldwide. Preterm babies of mothers with early onset preeclampsia (EOPE) are at higher risks for various diseases later on in life, including cardiovascular diseases. We hypothesized that genome-wide epigenetic alterations occur in cord blood DNAs in association with EOPE and conducted a case control study to compare the genome-scale methylome differences in cord blood DNAs between 12 EOPE-associated and 8 normal births. RESULTS: Bioinformatics analysis of methylation data from the Infinium HumanMethylation450 BeadChip shows a genome-scale hypomethylation pattern in EOPE, with 51,486 hypomethylated CpG sites and 12,563 hypermethylated sites (adjusted P <0.05). A similar trend also exists in the proximal promoters (TSS200) associated with protein-coding genes. Using summary statistics on the CpG sites in TSS200 regions, promoters of 643 and 389 genes are hypomethylated and hypermethylated, respectively. Promoter-based differential methylation (DM) analysis reveals that genes in the farnesoid X receptor and liver X receptor (FXR/LXR) pathway are enriched, indicating dysfunction of lipid metabolism in cord blood cells. Additional biological functional alterations involve inflammation, cell growth, and hematological system development. A two-way ANOVA analysis among coupled cord blood and amniotic membrane samples shows that a group of genes involved in inflammation, lipid metabolism, and proliferation are persistently differentially methylated in both tissues, including IL12B, FAS, PIK31, and IGF1. CONCLUSIONS: These findings provide, for the first time, evidence of prominent genome-scale DNA methylation modifications in cord blood DNAs associated with EOPE. They may suggest a connection between inflammation and lipid dysregulation in EOPE-associated newborns and a higher risk of cardiovascular diseases later in adulthood. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-015-0052-x) contains supplementary material, which is available to authorized users. BioMed Central 2015-03-13 /pmc/articles/PMC4371797/ /pubmed/25806090 http://dx.doi.org/10.1186/s13148-015-0052-x Text en © Ching et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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
Ching, Travers
Ha, James
Song, Min-Ae
Tiirikainen, Maarit
Molnar, Janos
Berry, Marla J
Towner, Dena
Garmire, Lana X
Genome-scale hypomethylation in the cord blood DNAs associated with early onset preeclampsia
title Genome-scale hypomethylation in the cord blood DNAs associated with early onset preeclampsia
title_full Genome-scale hypomethylation in the cord blood DNAs associated with early onset preeclampsia
title_fullStr Genome-scale hypomethylation in the cord blood DNAs associated with early onset preeclampsia
title_full_unstemmed Genome-scale hypomethylation in the cord blood DNAs associated with early onset preeclampsia
title_short Genome-scale hypomethylation in the cord blood DNAs associated with early onset preeclampsia
title_sort genome-scale hypomethylation in the cord blood dnas associated with early onset preeclampsia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371797/
https://www.ncbi.nlm.nih.gov/pubmed/25806090
http://dx.doi.org/10.1186/s13148-015-0052-x
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