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

Ching, Travers and Ha, James and Song, Min-Ae and Tiirikainen, Maarit and Molnar, Janos and Berry, Marla J. and Towner, Dena and Garmire, Lana X. (2015) Genome-scale hypomethylation in the cord blood DNAs associated with early onset preeclampsia. Clinical Epigenetics, 7 (1). Art. No. 21. ISSN 1868-7075. PMCID PMC4371797. https://resolver.caltech.edu/CaltechAUTHORS:20150421-101702823

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[img] PDF (Figure S1. Top 20 hypomethylated CpG sites. Dot plots of statistically significant top 20 hypomethylated CpG sites with Beta value difference greater than 0.2) - Supplemental Material
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[img] PDF (Figure S2. Top 20 hypermethylated CpG sites. Dot plots of statistically significant top 20 hypermethylated CpG sites) - Supplemental Material
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[img] MS Excel (Table S2. LincRNA pathway analysis. KEGG and BIOCARTA pathways with high correlations (ρ > 0.90) and significant P values (P < 0.05) for lincRNAs) - Supplemental Material
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[img] PDF (Figure S3. ANOVA plot of two factor analysis. Average F-statistics plot of tissue and disease factors using the summed TSS200 methylation Beta values in cord blood and paired chorioamniotic membrane samples) - Supplemental Material
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[img] MS Excel (Table S3. CpG sites related to preeclampsia and gestational age. A list of CpG from a comparison of the differentially methylated CpG sites in preeclampsia with the results of Cruickshank et al. [32] on gestational age) - Supplemental Material
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[img] MS Excel (Table S1. Pyrosequencing primers. A list of the primer sequences used to validate important CpG sites) - Supplemental Material
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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1186/s13148-015-0052-xDOIArticle
http://link.springer.com/article/10.1186/s13148-015-0052-xPublisherArticle
http://www.clinicalepigeneticsjournal.com/content/7/1/21PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371797/PubMed CentralArticle
Additional Information:© 2015 Ching et al.; licensee BioMed Central. 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. Received: 8 October 2014 Accepted: 5 February 2015. Published online 2015 Mar 13. This study was partially supported by RMATRIX award U54MD007584 and RCMI BRIDGES award G12 MD007601 from the National Institute on Minority Health and Health Disparities, National Institutes of Health (NIH) and research funding provided by the NIGMS P20 COBRE GM103457, NIEHS K01 ES025434-01, and Hawaiian Community Foundation to L.X. Garmire. M. Berry is supported by NIH grants RO1 DK047320 and G12 MD007601. The Genomics Shared Resource (GSR) at UHCC is supported by the P30-CA071789. We thank the University of Hawaii Biorepository team, including Dr. Abby Collier, Dr. Timothy Dye, Dr. Joshua Astern, Will Chen, and others for providing samples and resources. The University of Hawaii Biorepository is supported by the National Institute on Minority Health and Health Disparities U54MD007584, G12MD007601, and the National Institute of General Medical Sciences P20GM103466, from the National Institutes of Health.
Funders:
Funding AgencyGrant Number
National Institute of General Medical SciencesGM103457
National Institute of Environmental Health Sciences (NIEHS)K01 ES025434-01
Hawaiian Community FoundationUNSPECIFIED
NIHRO1 DK047320
National Cancer InstituteP30-CA071789
National Institute on Minority Health and Health DisparitiesU54MD007584
National Institute on Minority Health and Health DisparitiesG12MD007601
NIH P20GM103466
Subject Keywords:Preeclampsia, Epigenetics, DNA methylation, Cord blood, Bioinformatics
Issue or Number:1
PubMed Central ID:PMC4371797
Record Number:CaltechAUTHORS:20150421-101702823
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150421-101702823
Official Citation:Ching, T., Ha, J., Song, M.-A., Tiirikainen, M., Molnar, J., Berry, M. J., … Garmire, L. X. (2015). Genome-scale hypomethylation in the cord blood DNAs associated with early onset preeclampsia. Clinical Epigenetics, 7(1), 21. doi:10.1186/s13148-015-0052-x
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:56811
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:21 Apr 2015 18:16
Last Modified:03 Oct 2019 08:17

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