title: Unique DNA Methylation Patterns in Offspring of Hypertensive Pregnancy.
abstract: Epigenomic processes are believed to play a pivotal role for the effect of environmental exposures in early life to modify disease risk throughout the lifespan. Offspring of women with hypertensive complications of pregnancy (HTNPREG ) have an increased risk of developing systemic and pulmonary vascular dysfunction in adulthood. In this preliminary report, we sought to determine whether epigenetic modifications of genes involved in the regulation of vascular function were present in HTNPREG offspring. We contrasted DNA methylation and gene expression patterns of peripheral blood mononuclear cells obtained from young male offspring of HTNPREG (n = 5) to those of normotensive controls (n = 19). In HTNPREG offspring we identified six differentially methylated regions (DMRs) including three genes (SMOC2, ARID1B and CTRHC1) relevant to vascular function. The transcriptional activity of ARID1B and CTRCH1 was inversely related to methylation status. HTNPREG offspring had higher systolic pulmonary artery pressure (sPPA ) versus controls. Our findings demonstrate that epigenetic marks are altered in offspring of HTNPREG with a modest elevation of sPPA and introduce novel epigenomic targets for further study. On the basis of these findings we speculate that epigenomic mechanisms may be involved in mediating the effect of HTNPREG to raise the risk of vascular disease later in life.
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Colleen G
authors.initials: CG
authors.lastname: Julian
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Brent S
authors.initials: BS
authors.lastname: Pedersen
authors.affiliation: Bolivian Institute of High Altitude Biology, La Paz, Bolivia.
authors.forename: Carlos Salinas
authors.initials: CS
authors.lastname: Salmon
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Ivana V
authors.initials: IV
authors.lastname: Yang
authors.affiliation: Bolivian Institute of High Altitude Biology, La Paz, Bolivia.
authors.forename: Marcelino
authors.initials: M
authors.lastname: Gonzales
authors.affiliation: Bolivian Institute of High Altitude Biology, La Paz, Bolivia.
authors.forename: Enrique
authors.initials: E
authors.lastname: Vargas
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Lorna G
authors.initials: LG
authors.lastname: Moore
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
mesh_terms: D000328:Adult; D062186:Arterial Pressure; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006973:Hypertension / Q000150:complications*; D046110:Hypertension, Pregnancy-Induced / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008171:Lung Diseases / Q000235:genetics*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000175:diagnosis*; D011651:Pulmonary Artery / Q000473:pathology; D011667:Pulmonary Veins / Q000503:physiopathology; D012307:Risk Factors; D014652:Vascular Diseases / Q000235:genetics; D055815:Young Adult
keywords: developmental programming; epigenetics; gestational hypertension; preeclampsia