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Clin Epigenetics. 2015 Mar 13;7:21. doi: 10.1186/s13148-015-0052-x. eCollection 2015.

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

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Molecular Bioscience and Bioengineering Graduate Program, University of Hawaii at Manoa, Honolulu, HI 96822 USA.
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813 USA.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91126 USA.
Epidemiology Department, The Ohio State University, The College of Public Health, Columbus, OH 43210 USA.
University of Hawaii Cancer Center, The Ohio State University and James Cancer Hospital, Columbus, OH 43210 USA.
Genomics Shared Resources, University of Hawaii Cancer Center, Honolulu, HI 96813 USA.
Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813 USA.
Department of Obstetrics, Gynecology and Women's Health, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96826 USA.
Contributed equally



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.


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.


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.


Bioinformatics; Cord blood; DNA methylation; Epigenetics; Preeclampsia

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