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Published March 13, 2015 | Published + Supplemental Material
Journal Article Open

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 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.

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.

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August 20, 2023
August 20, 2023