From the Epidemiology Branch (T.W., M.O., D.S., K.L.G., F.T.-A.).
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD (J.W.).
Hypertension. 2020 Apr;75(4):1117-1124. doi: 10.1161/HYPERTENSIONAHA.119.14509. Epub 2020 Feb 10.
Abnormal blood pressure during pregnancy is associated with impaired fetal growth, predisposing the offspring to cardiometabolic abnormalities over the life-course. Placental DNA methylation may be the regulatory pathway through which maternal blood pressure influences fetal and adult health outcomes. Epigenome-wide association study of 301 participants with placenta sample examined associations between DNA methylation and millimetre of mercury increases in systolic and diastolic blood pressure in each trimester. Findings were further examined using gene expression, gene pathway, and functional annotation analyses. Cytosine-(phosphate)-guanine (CpGs) known to be associated with cardiometabolic traits were evaluated. Increased maternal systolic and diastolic blood pressure were associated with methylation of 3 CpGs in the first, 6 CpGs in the second, and 15 CpGs in the third trimester at 5% false discovery rate ( values ranging from 6.6×10 to 2.3×10). Several CpGs were enriched in pathways including cardiovascular-metabolic development (=1.0×10). Increased systolic and diastolic blood pressure were associated with increased CpG methylation and gene expression at , a collagen family gene known for regulatory functions in the heart. Out of 304 previously reported CpGs known to be associated with cardiometabolic traits, 36 placental CpGs were associated with systolic and diastolic blood pressure in our data. The present study provides the first evidence for associations between placental DNA methylation and increased maternal blood pressure during pregnancy at genes implicated in cardiometabolic diseases. Identification of blood pressure-associated methylated sites in the placenta may provide clues to early origins of cardiometabolic dysfunction and inform guidelines for early prevention. Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00912132.
妊娠期血压异常与胎儿生长受损有关，使后代在整个生命过程中易患心脏代谢异常。胎盘 DNA 甲基化可能是调节母体血压影响胎儿和成人健康结果的途径。对 301 名有胎盘样本的参与者进行的全基因组关联研究，研究了每个孕期收缩压和舒张压毫米汞柱升高与 DNA 甲基化之间的关联。使用基因表达、基因途径和功能注释分析进一步检查了研究结果。评估了与心脏代谢特征相关的已知胞嘧啶（磷酸）鸟嘌呤（CpG）。在 5%的假发现率（ 值范围从 6.6×10 到 2.3×10）下，母体收缩压和舒张压升高与第一个孕期的 3 个 CpG、第二个孕期的 6 个 CpG 和第三个孕期的 15 个 CpG 的甲基化有关。几个 CpG 在包括心血管代谢发育在内的途径中富集（=1.0×10）。收缩压和舒张压升高与 基因的 CpG 甲基化和基因表达增加有关， 基因是心脏中具有调节功能的胶原家族基因。在 304 个先前报道的与心脏代谢特征相关的 CpG 中，有 36 个胎盘 CpG 与我们数据中母亲怀孕期间的收缩压和舒张压相关。本研究首次提供了证据，证明了与心脏代谢疾病相关的基因中胎盘 DNA 甲基化与妊娠期间母体血压升高之间存在关联。鉴定胎盘与血压相关的甲基化位点可能为心脏代谢功能障碍的早期起源提供线索，并为早期预防提供指导方针。注册- URL：http://www.clinicaltrials.gov。独特标识符：NCT00912132。
