Division of Pulmonary, Allergy, Critical Care Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, PH8E-101, 630 W. 168 St., New York, NY 10032 USA.
Division of Pediatric Pulmonary, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, 630 W. 168 St., New York, NY 10032 USA.
Clin Epigenetics. 2017 Jun 2;9:61. doi: 10.1186/s13148-017-0361-3. eCollection 2017.
Asthma gene DNA methylation may underlie the effects of air pollution on airway inflammation. However, the temporality and individual susceptibility to environmental epigenetic regulation of asthma has not been fully elucidated. Our objective was to determine the timeline of black carbon (BC) exposure, measured by personal sampling, on DNA methylation of allergic asthma genes 5 days later to capture usual weather variations and differences related to changes in behavior and activities. We also sought to determine how methylation may vary by seroatopy and cockroach sensitization and by elevated fractional exhaled nitric oxide (FeNO).
Personal BC levels were measured during two 24-h periods over a 6-day sampling period in 163 New York City children (age 9-14 years), repeated 6 months later. During home visits, buccal cells were collected as noninvasive surrogates for lower airway epithelial cells and FeNO measured as an indicator of airway inflammation. CpG promoter loci of allergic asthma genes (e.g., interleukin 4 (IL4), interferon gamma (IFNγ), inducible nitric oxide synthase (NOS2A)), arginase 2 (ARG2)) were pyrosequenced at the start and end of each sampling period.
Higher levels of BC were associated with lower methylation of IL4 promoter CpG 5 days later. The magnitude of association between BC exposure and demethylation of IL4 CpG and NOS2A CpG measured 5 days later appeared to be greater among seroatopic children, especially those sensitized to cockroach allergens (RR [95% CI] 0.55 [0.37-0.82] and 0.67 [0.45-0.98] for IL4 CpG and NOS2A CpG, respectively), compared to non-sensitized children (RR [95% CI] 0.87 [0.65-1.17] and 0.95 [0.69-1.33] for IL4 CpG and NOS2A CpG, respectively); however, the difference was not statistically different. In multivariable linear regression models, lower DNA methylation of IL4 CpG and NOS2A CpG were associated with increased FeNO.
Our results suggest that exposure to BC may exert asthma proinflammatory gene demethylation 5 days later that in turn may link to airway inflammation. Our results further suggest that seroatopic children, especially those sensitized to cockroach allergens, may be more susceptible to the effect of acute BC exposure on epigenetic changes.
哮喘基因的 DNA 甲基化可能是空气污染对气道炎症影响的基础。然而，环境对哮喘的表观遗传调控的时间性和个体易感性尚未完全阐明。我们的目的是确定通过个人采样测量的黑碳 (BC) 暴露的时间线，以便在 5 天后捕获通常的天气变化以及与行为和活动变化相关的差异。我们还试图确定 DNA 甲基化如何因血清阳性和蟑螂致敏以及呼出气一氧化氮分数升高而发生变化。
在为期 6 天的采样期内，163 名纽约市儿童（9-14 岁）进行了两次为期 24 小时的个人 BC 水平测量，6 个月后重复测量。在家庭访问期间，采集口腔细胞作为下呼吸道上皮细胞的非侵入性替代物，并测量呼出气一氧化氮（FeNO）作为气道炎症的指标。在每个采样期开始和结束时，对过敏性哮喘基因（例如白细胞介素 4 (IL4)、干扰素 γ (IFNγ)、诱导型一氧化氮合酶 (NOS2A)）的 CpG 启动子位点进行焦磷酸测序，精氨酸酶 2 (ARG2)。
较高的 BC 水平与 5 天后 IL4 启动子 CpG 的去甲基化相关。BC 暴露与 IL4 CpG 和 NOS2A CpG 5 天后去甲基化之间的关联程度，在血清阳性的儿童中，尤其是对蟑螂过敏原敏感的儿童中，似乎更大（IL4 CpG 和 NOS2A CpG 的比值比 [95%CI] 分别为 0.55 [0.37-0.82] 和 0.67 [0.45-0.98]），而非致敏儿童（IL4 CpG 和 NOS2A CpG 的比值比 [95%CI] 分别为 0.87 [0.65-1.17] 和 0.95 [0.69-1.33]）；然而，差异无统计学意义。在多变量线性回归模型中，IL4 CpG 和 NOS2A CpG 的 DNA 低甲基化与 FeNO 升高相关。
我们的结果表明，BC 暴露可能在 5 天后使哮喘促炎基因发生去甲基化，进而可能与气道炎症有关。我们的结果进一步表明，血清阳性的儿童，尤其是对蟑螂过敏原敏感的儿童，可能更容易受到急性 BC 暴露对表观遗传变化的影响。
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