Genome-wide methylation profiling demonstrates hypermethylation in maternal leukocyte DNA in preeclamptic compared to normotensive pregnancies

Abstract

Objective: To compare genome-wide methylation profiles in maternal leukocyte DNA between normotensive and preeclamptic pregnant women at delivery. Methods: Age, body mass index matched case-control comparison of methylation at 27,578 cytosine— guanine sites in 14,495 genes in maternal leukocyte DNA in women with preeclampsia (PE; n = 14) and normotensive controls (n = 14). Results: PE was associated with widespread differential methylation favoring hypermethylation. Pathway analysis identified the best matched process as a neuropeptide signaling pathway (p < 10⁻⁵); best matched disease as eclampsia (p < 9.97 × 10⁻²⁰). Significantly differentially methylated genes (GRIN2b. GABRA1. PCDHB7, and BEX1) are associated with seizures. Conclusion: Altered maternal leukocyte DNA methylation is associated with PE at delivery, and differential methylation of certain neuronal genes may explain the risk for eclampsia.

• DNA methylation
• Epigenetics
• Leukocyte
• Maternal
• Pregnancy
• Preeclampsia.

Acknowledgments

We thank the Mayo Clinic Center for Individualized Medicine for access to the Biobank samples.

Funding

This work was funded by the Mayo Clinic Foundation: Mary Kathryn and Michael B. Panitch Career Development Award and K08HD051714 (Vesna D. Garovic) from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health & Human Development or the National Institutes of Health.

Methylation data can be found at http://www.ncbi.nlm.nih.gov/geo/ using

GEO submission ID: GSE37722.