Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, New York, United States of America.
PLoS One. 2013 Sep 4;8(9):e72824. doi: 10.1371/journal.pone.0072824. eCollection 2013.
DNA methylation changes have been implicated in many common chronic diseases leading to the hypothesis that environmental and age-related DNA methylation changes within individuals are involved in disease etiology. Few studies have examined DNA methylation changes within an individual over time and all of these studies have been conducted in adults. Here, we aim to characterize how global DNA methylation changes from birth to age three within a longitudinal birth cohort study and to determine whether there are consistent predictors of DNA methylation levels measured three years apart. We measured global DNA methylation in the same children at birth (cord blood) and again at three years of age among 165 children, using an immunoassay. We found that on average, DNA methylation was significantly higher in blood at age 3-years than in cord blood (p<0.01). However, for any individual child, the difference was less than would be expected by chance. We found that pre-pregnancy BMI was negatively predictive of both cord and three-year DNA methylation, even after statistical adjustment to account for the correlation between cord blood and three-year DNA methylation. The biologic implications of small changes in global DNA methylation are unknown. However, the observation that global DNA methylation levels persist within an individual from birth to age three supports the belief that factors that influence global DNA methylation, including pre-pregnancy BMI, may confer long-term effects.
DNA 甲基化变化与许多常见的慢性疾病有关，这导致了一个假设，即个体内部的环境和与年龄相关的 DNA 甲基化变化可能与疾病的病因有关。很少有研究在个体内部随时间观察 DNA 甲基化变化，而且所有这些研究都是在成年人中进行的。在这里，我们旨在描述在纵向出生队列研究中个体从出生到 3 岁期间的全基因组 DNA 甲基化变化，并确定是否存在一致的 DNA 甲基化水平的预测因子，这些水平在相隔三年的时间内进行测量。我们使用免疫测定法在 165 名儿童中测量了他们在出生时（脐带血）和三岁时的全基因组 DNA 甲基化。我们发现，平均而言，3 岁时血液中的 DNA 甲基化水平明显高于脐带血（p<0.01）。然而，对于任何一个孩子，这种差异都小于预期的偶然差异。我们发现，孕前 BMI 与脐带血和三岁时的 DNA 甲基化均呈负相关，即使在统计上调整了脐带血和三岁时 DNA 甲基化之间的相关性。全基因组 DNA 甲基化的微小变化的生物学意义尚不清楚。然而，从出生到 3 岁，个体内部的全基因组 DNA 甲基化水平保持不变的观察结果支持了这样一种信念，即影响全基因组 DNA 甲基化的因素，包括孕前 BMI，可能会产生长期影响。
