Genome-Wide Identification of Epigenetic Hotspots Potentially Related to Cardiovascular Risk in Adult Women after a Complicated Pregnancy

Abstract

BackgroundThe physiological demands of pregnancy on the maternal cardiovascular system can catapult women into a metabolic syndrome that predisposes to atherosclerosis in later life. We sought to identify the nature of the epigenomic changes associated with the increased cardiovascular disease (CVD) risk in adult women following pre-eclampsia.FindingsWe assessed the genome wide epigenetic profile by methyl-C sequencing of monozygotic parous twin sister pairs discordant for a severe variant of pre-eclampsia. In the adult twin sisters at risk for CVD as a consequence of a complicated pregnancy, a set of 12 differentially methylated regions with at least 50% difference in methylation percentage and the same directional change was found to be shared between the affected twin sisters and significantly different compared to their unaffected monozygous sisters.ConclusionThe current epigenetic marker set will permit targeted analysis of differentially methylated regions potentially related to CVD risk in large cohorts of adult women following complicated pregnancies.

Association between DNA methylation and coronary heart disease or other atherosclerotic events: A systematic review

“…In total, 51 articles met our eligibility criteria (Supplementary Table 1) and were included in the analysis. Of the 51 selected studies, 17 included participants from Europe [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] 14 from China [23][24][25][26][27][28][29][30][31][32][33][34][35][36], six from USA [37][38][39][40][41][42], three from India [43][44][45], two from Canada [46,47], and one each from Japan [48], Malaysia [49], Iran [50], Russia [51], Brazil [52] and Mexico [53]…”

“…Seven studies analyzed global DNA methylation [6,7,23,34,36,42,52], 31 followed a candidate-gene approach [8][9][10][11][12][13][14]20,22,[24][25][26][27][28][29][30][31][32][33]35,[38][39][40][41]45,46,49,50,[54][55][56], seven were epigenome-wide association studies (EWAS) [16,18,19,21,44,48,53], two used both global DNA methylation and candidate-gene approaches [37,43], three used EWAS and global DNA methylation approaches [15,17,51], and on...…”

“…The Infinium Human Methylation 450 BeadChip Array (Illumina) was the most commonly used array ( Supplementary Table 2c) [15][16][17]19,47,48]. Most of the selected EWAS analyzed blood samples (n=7) [16][17][18][19]21,43,47], and the others analyzed vascular tissues [15,48,53] (Supplementary Table 2c).…”

“…Four EWAS only showed results of the discovery cohort without any validation of the main findings [18,19,47,48]. Samples from more than 100 individuals were analyzed in the discovery phase of three EWAS [16,17,19] and in the validation phase of three EWAS [16,17,21].…”

“…Samples from more than 100 individuals were analyzed in the discovery phase of three EWAS [16,17,19] and in the validation phase of three EWAS [16,17,21]. Two EWAS included samples from fewer than 10 individuals in the discovery phase [18,51]. Some studies discovered differentially methylated CpG sites, while others found regions ("islands") with a high frequency of CpG sites (Supplementary Table 4).…”