Department of Pediatrics, Women & Infants Hospital, Brown University, Providence, RI, USA.
Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, NC, USA.
Pediatr Res. 2022 May;91(6):1469-1477. doi: 10.1038/s41390-021-01531-5. Epub 2021 May 5.
There is increased risk of cardiovascular, metabolic, and hypertensive disorders in later life in the preterm population. We studied school-age children who had been born extremely premature who had undergone endocrine, cardiovascular, and anthropometric evaluations.
School age measurements of salivary cortisol, adrenal androgens, blood pressure, and anthropometric markers were correlated with DNA methylation of 11-betahydroxysteroid dehydrogenase type 2 (11BHSD2), leptin, and the LINE1 repetitive DNA element.
We observed a modest correlation between log AUC for salivary cortisol and methylation of leptin in preterm infants and a negative correlation between methylation of region 1 of the glucocorticoid receptor (GR in term-born infants. There was an association between LINE1 methylation and cortisol response to awakening and a negative correlation between LINE1 and systolic blood pressure at 6-7 years. Methylation of the GR promoter region showed a positive association with systolic blood pressure at 6-7 years of age.
These results show that extremely preterm birth, followed by complex patterns of endocrine, cardiovascular, and metabolic exposures during early postnatal life, is associated with lasting changes in DNA methylation patterns in genes involved in hypothalamic pituitary adrenal axis function, adrenal hormonal regulation, and cardiometabolic risk.
Preterm infants have significant environmental and physiological exposures during early life that may have lasting impact on later function. Alterations in hypothalamic pituitary adrenal axis (HPA) function have been associated with these exposures. We examined the associated changes in DNA methylation of important genes involved in HPA function, metabolism, and global DNA methylation. The changes we saw in DNA methylation may help to explain associated cardiovascular, metabolic, and growth disturbance in these children in later life.
早产儿在以后的生活中患心血管、代谢和高血压疾病的风险增加。我们研究了曾接受过内分泌、心血管和人体测量评估的极早产儿的学龄儿童。
将唾液皮质醇、肾上腺雄激素、血压和人体测量标记物的学龄测量值与 11-β羟类固醇脱氢酶 2（11BHSD2）、瘦素和 LINE1 重复 DNA 元件的 DNA 甲基化相关联。
我们观察到早产儿唾液皮质醇 AUC 对数与瘦素甲基化之间存在中度相关性，足月出生婴儿的糖皮质激素受体（GR）第 1 区甲基化呈负相关。LINE1 甲基化与觉醒时皮质醇反应之间存在关联，LINE1 与 6-7 岁时的收缩压呈负相关。GR 启动子区域的甲基化与 6-7 岁时的收缩压呈正相关。
这些结果表明，极早产儿出生后，在早期新生儿期经历复杂的内分泌、心血管和代谢暴露，与参与下丘脑-垂体-肾上腺轴功能、肾上腺激素调节和心脏代谢风险的基因中的 DNA 甲基化模式的持久变化相关。
早产儿在生命早期有显著的环境和生理暴露，这可能对以后的功能有持久的影响。下丘脑-垂体-肾上腺轴（HPA）功能的改变与这些暴露有关。我们检查了参与 HPA 功能、代谢和全球 DNA 甲基化的重要基因的相关 DNA 甲基化变化。我们在 DNA 甲基化中看到的变化可能有助于解释这些儿童以后生活中与心血管、代谢和生长障碍相关的变化。
