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10.1093/molehr/gau046

http://scihub22266oqcxt.onion/10.1093/molehr/gau046
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C4131767!4131767!24944161
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suck abstract from ncbi


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pmid24944161      Mol+Hum+Reprod 2014 ; 20 (9): 885-904
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  • Genome-wide hypermethylation coupled with promoter hypomethylation in the chorioamniotic membranes of early onset pre-eclampsia #MMPMID24944161
  • Ching T; Song MA; Tiirikainen M; Molnar J; Berry M; Towner D; Garmire LX
  • Mol Hum Reprod 2014[Sep]; 20 (9): 885-904 PMID24944161show ga
  • Pre-eclampsia is the leading cause of fetal and maternal morbidity and mortality. Early onset pre-eclampsia (EOPE) is a disorder that has severe maternal and fetal outcomes, whilst its etiology is poorly understood. We hypothesize that epigenetics plays an important role to mediate the development of EOPE and conducted a case?control study to compare the genome-wide methylome difference between chorioamniotic membranes from 30 EOPE and 17 full-term pregnancies using the Infinium Human Methylation 450 BeadChip arrays. Bioinformatics analysis tested differential methylation (DM) at CpG site level, gene level, and pathway and network level. A striking genome-wide hypermethylation pattern coupled with hypomethylation in promoters was observed. Out of 385 184 CpG sites, 9995 showed DM (2.6%). Of those DM sites, 91.9% showed hypermethylation (9186 of 9995). Over 900 genes had DM associated with promoters. Promoter-based DM analysis revealed that genes in canonical cancer-related pathways such as Rac, Ras, PI3K/Akt, NF?B and ErBB4 were enriched, and represented biological functional alterations that involve cell cycle, apoptosis, cancer signaling and inflammation. A group of genes previously found to be up-regulated in pre-eclampsia, including GRB2, ATF3, NFKB2, as well as genes in proteasome subunits (PSMA1, PMSE1, PSMD1 and PMSD8), harbored hypomethylated promoters. Contrarily, a cluster of microRNAs, including mir-519a1, mir-301a, mir-487a, mir-185, mir-329, mir-194, mir-376a1, mir-486 and mir-744 were all hypermethylated in their promoters in the EOPE samples. These findings collectively reveal new avenues of research regarding the vast epigenetic modifications in EOPE.
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