Supplemental Digital Content is available in the text. 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 (P values ranging from 6.6×10−15 to 2.3×10−7). Several CpGs were enriched in pathways including cardiovascular-metabolic development (P=1.0×10−45). Increased systolic and diastolic blood pressure were associated with increased CpG methylation and gene expression at COL12A1, 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.

中文翻译：

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胎盘差异 DNA 甲基化与孕期母体血压相关


文本中提供了补充数字内容。怀孕期间血压异常与胎儿生长受损有关，使后代在整个生命过程中容易出现心脏代谢异常。胎盘 DNA 甲基化可能是母体血压影响胎儿和成人健康结果的调节途径。对 301 名胎盘样本参与者进行的表观基因组关联研究检查了 DNA 甲基化与每个妊娠期收缩压和舒张压升高毫米汞柱之间的关联。使用基因表达、基因通路和功能注释分析进一步检查研究结果。对已知与心脏代谢特征相关的胞嘧啶-（磷酸）-鸟嘌呤（CpG）进行了评估。母亲收缩压和舒张压升高与第一期 3 个 CpG、第二期 6 个 CpG、晚期妊娠 15 个 CpG 甲基化相关，错误发现率为 5%（P 值范围为 6.6×10−15 至 2.3×） 10−7).一些 CpG 在心血管代谢发育等途径中富集 (P=1.0×10−45)。收缩压和舒张压的升高与 CpG 甲基化和 COL12A1 基因表达的增加有关，COL12A1 是一种以心脏调节功能而闻名的胶原蛋白家族基因。在我们的数据中，在之前报道的 304 个已知与心脏代谢特征相关的 CpG 中，有 36 个胎盘 CpG 与收缩压和舒张压相关。本研究提供了第一个证据，证明胎盘 DNA 甲基化与妊娠期间母体血压升高之间存在关联，这些基因与心脏代谢疾病有关。 胎盘中与血压相关的甲基化位点的识别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。注册 — URL：http://www.clinicaltrials.gov。唯一标识符：NCT00912132。