DNA methylation is altered in maternal blood vessels of women with preeclampsia.
We analyzed 27,578 CpG sites that map to 14,495 genes in omental arteries of normal pregnant and preeclamptic women for DNA methylation status using the Illumina platform. We found 1685 genes with a significant difference in DNA methylation at a false discovery rate of <10% with many inflammatory genes having reduced methylation. Unsupervised hierarchical clustering revealed natural clustering by diagnosis and methylation status. Of the genes with significant methylation differences, 236 were significant at a false discovery rate of <5%. When data were analyzed more stringently to a false discovery rate of <5% and difference in methylation of >0.10, 65 genes were identified, all of which showed reduced methylation in preeclampsia. When these genes were mapped to gene ontology for molecular functions and biological processes, 75 molecular functions and 149 biological processes were overrepresented in the preeclamptic vessels. These included smooth muscle contraction, thrombosis, inflammation, redox homeostasis, sugar metabolism, and amino acid metabolism. We speculate that reduced methylation may contribute to the pathogenesis of preeclampsia and that alterations in DNA methylation resulting from preeclampsia may increase maternal risk of cardiovascular disease later in life.
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Ahmad A
AA
Mousa
Kellie J
KJ
Archer
Renato
R
Cappello
Guadalupe
G
Estrada-Gutierrez
Christine R
CR
Isaacs
Jerome F
JF
Strauss
Scott W
SW
Walsh
D000328:Adult; D000596:Amino Acids / Q000378:metabolism; D001158:Arteries / Q000503:physiopathology*; D050260:Carbohydrate Metabolism; D019175:DNA Methylation / Q000235:genetics / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000502:physiology; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009852:Omentum / Q000098:blood supply; D010084:Oxidation-Reduction; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D013927:Thrombosis / Q000503:physiopathology
D000596:Amino Acids