Unique DNA Methylation Patterns in Offspring of Hypertensive Pregnancy

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 (HTN_PREG) 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 HTN_PREG offspring. We contrasted DNA methylation and gene expression patterns of peripheral blood mononuclear cells obtained from young male offspring of HTN_PREG (n = 5) to those of normotensive controls (n = 19). In HTN_PREG 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. HTN_PREG offspring had higher systolic pulmonary artery pressure (sP_PA) versus controls. Our findings demonstrate that epigenetic marks are altered in offspring of HTN_PREG with a modest elevation of sP_PA 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 HTN_PREG to raise the risk of vascular disease later in life.