Researchers have found the first associations between BP during pregnancy and placental DNA methylation at genes linked to fetal development and CVD later in life.
According to research published Hypertension, elevated maternal BP was associated with methylation of three cytosine-(phosphate)-guanine sites in the first trimester, six sites in the second trimester and 15 sites during the third trimester (5% false discovery rate; P values from 6.6 × 10-15 to 2.3 × 10-7). Multiple cytosine-(phosphate)-guanine sites were enriched in pathways including those associated with cardiometabolic development (P = 1 × 10-45), according to the study.
Of 304 cytosine-(phosphate)-guanine sites known to be associated with cardiometabolic traits, approximately 12% of placental sites were associated with systolic or diastolic BP, according to the study.
“The placenta is increasingly being recognized to be sensitive to intrauterine exposures; however, to our knowledge, no previous study has examined whether maternal BP is linked with DNA methylation changes at a genome-wide scale,” Fasil Tekola-Ayele, PhD, Earl Stadtman investigator in the epidemiology branch of the division of intramural population health research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, told Healio. “This study begins to fill that gap, successfully identifying loci sensitive to maternal BP across the three trimesters of pregnancy and potential overlaps with CV outcomes. Studies with larger sample sizes are needed to identify additional loci related with BP.”
Moreover, elevated maternal BP was associated with increased cytosine-(phosphate)-guanine site methylation and gene expression at COL12A1, a gene linked to regulatory function of the heart.
“[These findings] provide strong evidence for placental DNA methylation of genes involved in cardiovascular-metabolic development pathways,” the researchers wrote. “Placental cytosine-(phosphate)-guanine sites that were known to be associated with cardiometabolic factors in other studies, conferred associations with systolic and diastolic BP in our data. Findings on blood pressure-associated methylated sites in the placenta may provide clues to early origins of cardiometabolic disease risk and inform guidelines for early prevention.”
Researchers analyzed placenta samples of 301 participants and investigated the association between DNA methylation and BP elevations each trimester. According to the study, data were further examined using gene expression, gene pathway and functional annotation analyses.
“Functional studies are needed to shed light on the mechanisms that underlie these findings, and to clarify whether the overlaps with CVD are due to trans-tissue and persistent effects on the epigenome,” Tekola-Ayele said in an interview. – by Scott Buzby
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Fasil Tekola-Ayele, PhD, can be reached at firstname.lastname@example.org.
Disclosures: The authors report no relevant financial disclosures.