BACKGROUND Evidence suggests that prenatal air pollution exposure alters DNA methylation (DNAm), which could go on to affect long-term health. It remains unclear whether DNAm alterations present at birth persist through early life. Identifying persistent DNAm changes would provide greater insight into the molecular mechanisms contributing to the association of prenatal air pollution exposure with atopic diseases. OBJECTIVES This study investigated DNAm differences associated with prenatal nitrogen dioxide (NO2) exposure (a surrogate measure of traffic-related air pollution) at birth and 1 y of age and examined their role in atopic disease. We focused on regions showing persistent DNAm differences from birth to 1 y of age and regions uniquely associated with postnatal NO2 exposure. METHODS Microarrays measured DNAm at birth and at 1 y of age for an atopy-enriched subset of Canadian Health Infant Longitudinal Development (CHILD) study participants. Individual and regional DNAm differences associated with prenatal NO2 (n=128) were identified, and their persistence at age 1 y were investigated using linear mixed effects models (n=124). Postnatal-specific DNAm differences (n=125) were isolated, and their association with NO2 in the first year of life was examined. Causal mediation investigated whether DNAm differences mediated associations between NO2 and age 1 y atopy or wheeze. Analyses were repeated using biological sex-stratified data. RESULTS At birth (n=128), 18 regions of DNAm were associated with NO2, with several annotated to HOX genes. Some of these regions were specifically identified in males (n=73), but not females (n=55). The effect of prenatal NO2 across CpGs within altered regions persisted at 1 y of age. No significant mediation effects were identified. Sex-stratified analyses identified postnatal-specific DNAm alterations. DISCUSSION Regional cord blood DNAm differences associated with prenatal NO2 persisted through at least the first year of life in CHILD participants. Some differences may represent sex-specific alterations, but replication in larger cohorts is needed. The early postnatal period remained a sensitive window to DNAm perturbations. https://doi.org/10.1289/EHP13034.

中文翻译：

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加拿大预期出生研究中生命第一年和产前 NO2 暴露的持续 DNA 甲基化变化。


背景证据表明，产前接触空气污染会改变 DNA 甲基化 (DNAm)，这可能会继续影响长期健康。目前尚不清楚出生时出现的 DNAm 改变是否会持续到生命早期。识别持续的 DNAm 变化将有助于更深入地了解导致产前空气污染暴露与特应性疾病之间关系的分子机制。目的 本研究调查了出生时和 1 岁时与产前二氧化氮 (NO2) 暴露（交通相关空气污染的替代指标）相关的 DNAm 差异，并检验了它们在特应性疾病中的作用。我们重点关注从出生到 1 岁表现出持续 DNAm 差异的区域以及与出生后 NO2 暴露独特相关的区域。方法 微阵列测量了加拿大健康婴儿纵向发育 (CHILD) 研究参与者中富含特应性的子集在出生时和 1 岁时的 DNAm。确定了与产前 NO2 (n=128) 相关的个体和区域 DNAm 差异，并使用线性混合效应模型研究了它们在 1 岁时的持续性 (n=124)。分离出产后特异性 DNAm 差异 (n=125)，并检查它们与出生第一年 NO2 的关联。因果调节研究了 DNAm 差异是否介导 NO2 与 1 岁过敏症或喘息之间的关联。使用生物性别分层数据重复分析。结果 出生时 (n=128)，DNAm 的 18 个区域与 NO2 相关，其中几个区域被注释为 HOX 基因。其中一些区域在男性 (n=73) 中被明确识别，但在女性 (n=55) 中没有被明确识别。产前 NO2 对改变区域内 CpG 的影响持续到 1 岁。没有发现显着的中介效应。 性别分层分析确定了产后特异性 DNAm 改变。讨论 与产前 NO2 相关的区域脐带血 DNAm 差异至少持续到儿童参与者生命的第一年。一些差异可能代表性别特异性的改变，但需要在更大的队列中进行复制。产后早期仍然是 DNAm 扰动的敏感窗口。 https://doi.org/10.1289/EHP13034。