Rutgers, The State University of New Jersey, 170 Frelinghuysen Rd, Room 204, Piscataway, NJ, 08854, USA.
The New School, New York, NY, USA.
Environ Health. 2021 Feb 11;20(1):12. doi: 10.1186/s12940-020-00678-8.
Traffic-related air pollution (TRAP) has been associated with increased risk of airway inflammation in children with asthma. While epigenetic changes could potentially modulate TRAP-induced inflammatory responses, few studies have assessed the temporal pattern of exposure to TRAP, epigenetic changes and inflammation in children with asthma. Our goal was to test the time-lag patterns of personal exposure to TRAP, airway inflammation (measured as fractional exhaled nitric oxide, FeNO), and DNA methylation in the promoter regions of genes involved in nitric oxide synthesis among children with asthma.
We measured personal exposure to black carbon (BC) and FeNO for up to 30 days in a panel of children with asthma. We collected 90 buccal cell samples for DNA methylation analysis from 18 children (5 per child). Methylation in promoter regions of nitric oxide synthase (NOS1, NOS2A, NOS3) and arginase (ARG1, ARG2) was assessed by bisulfite pyrosequencing. Linear-mixed effect models were used to test the associations of BC at different lag periods, percent DNA methylation at each site and FeNO level.
Exposure to BC was positively associated with FeNO, and negatively associated with DNA methylation in NOS3. We found strongest association between FeNO and BC at lag 0-6 h while strongest associations between methylation at positions 1 and 2 in NOS3 and BC were at lag 13-24 h and lag 0-24 h, respectively. The strengths of associations were attenuated at longer lag periods. No significant associations between exposure to TRAP and methylation levels in other NOS and ARG isoforms were observed.
Exposure to TRAP was associated with higher levels of FeNO and lower levels of DNA methylation in the promoter regions of the NOS3 gene, indicating that DNA methylation of the NOS3 gene could be an important epigenetic mechanism in physiological responses to TRAP in children with asthma.
交通相关的空气污染（TRAP）已被证实与儿童哮喘的气道炎症风险增加有关。虽然表观遗传变化可能调节 TRAP 诱导的炎症反应，但很少有研究评估儿童哮喘患者暴露于 TRAP、表观遗传变化和炎症之间的时间模式。我们的目标是检测儿童哮喘患者中 TRAP 个人暴露、气道炎症（以呼出气一氧化氮分数表示，FeNO）和参与一氧化氮合成的基因启动子区域的 DNA 甲基化的时间滞后模式。
我们在一组哮喘儿童中测量了长达 30 天的个人暴露于黑碳（BC）和 FeNO 的情况。我们从 18 名儿童中采集了 90 个口腔细胞样本进行 DNA 甲基化分析（每个儿童 5 个样本）。通过亚硫酸氢盐焦磷酸测序评估一氧化氮合酶（NOS1、NOS2A、NOS3）和精氨酸酶（ARG1、ARG2）启动子区域的甲基化情况。线性混合效应模型用于检测不同滞后期 BC 与每个位点的百分比 DNA 甲基化和 FeNO 水平之间的关联。
BC 暴露与 FeNO 呈正相关，与 NOS3 中的 DNA 甲基化呈负相关。我们发现 FeNO 与 BC 之间最强的关联发生在滞后 0-6 小时，而 NOS3 中位置 1 和 2 的甲基化与 BC 之间最强的关联分别发生在滞后 13-24 小时和滞后 0-24 小时。随着滞后时间的延长，关联强度减弱。在其他 NOS 和 ARG 同工型中，未观察到 TRAP 暴露与甲基化水平之间存在显著关联。
TRAP 暴露与儿童哮喘患者 NOS3 基因启动子区域的 FeNO 水平升高和 DNA 甲基化水平降低有关，这表明 NOS3 基因的 DNA 甲基化可能是儿童哮喘患者对 TRAP 生理反应的重要表观遗传机制。
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