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An environmental epigenetic study of ADRB2 5′-UTR methylation and childhood asthma severity

机译：ADRB2 5'-UTR甲基化与儿童哮喘严重程度的环境表观遗传研究

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Background: Beta-2 adrenergic receptor (ADRB2) is the primary target of both short- and long-acting beta-agonist asthma medications. ADRB2 5′-UTR methylation changes in blood have the potential to act as a surrogate biomarker of responsiveness to beta-agonist treatment and childhood asthma severity. Objective: To study the association between ADRB2 5′-UTR methylation, NO 2 exposure and childhood asthma severity. Methods: We compared ADRB2 5′-UTR methylation levels in blood between 60 children with mild asthma and 122 children with severe asthma using methylation-specific PCR. We also investigated potential joint effects between NO 2 exposure and ADRB2 5′-UTR methylation. Results: We found a significant association between intermediate (OR: 4.11, 95% CI: 1.58-10.73) and high levels (OR: 7.63, 95% CI: 3.02-19.26) of ADRB2 methylation and severe childhood asthma. In addition, we found a significant association between indoor exposure to NO 2, an air pollutant and known asthmogen, and severe asthma among children exhibiting high ADRB2 methylation (OR: 4.59, 95% CI: 1.03-20.55) but no association among children exhibiting low levels of ADRB2 methylation (OR: 0.35, 95% CI: 0.01-14.13). Conclusions and Clinical Relevance: These findings support the potential use of ADRB2 5′-UTR methylation as a biomarker of both asthma severity and risk for NO 2-associated asthma exacerbations in children, and present the first evidence of an epigenetic link between an important environmental exposure and childhood asthma severity.
机译：背景：β2肾上腺素能受体（ADRB2）是长效和β受体激动剂哮喘药物的主要靶标。血液中的ADRB2 5'-UTR甲基化变化有可能充当对β受体激动剂治疗和儿童哮喘严重程度反应的替代生物标志物。目的：研究ADRB2 5'-UTR甲基化，NO 2暴露与儿童哮喘严重程度的关系。方法：我们使用甲基化特异性PCR比较了60例轻度哮喘儿童和122例严重哮喘儿童的血液中ADRB2 5'-UTR甲基化水平。我们还研究了NO 2暴露与ADRB2 5'-UTR甲基化之间的潜在联合效应。结果：我们发现中等水平（OR：4.11，95％CI：1.58-10.73）与高水平（OR：7.63，95％CI：3.02-19.26）的ADRB2甲基化与严重的儿童哮喘之间存在显着相关性。此外，我们发现室内暴露于NO 2（一种空气污染物和已知的哮喘原）的儿童与ADRB2甲基化程度较高的儿童（OR：4.59，95％CI：1.03-20.55）的严重哮喘之间存在显着关联，而在表现出ADRB2甲基化的儿童中则没有关联低水平的ADRB2甲基化（OR：0.35，95％CI：0.01-14.13）。结论和临床意义：这些发现支持将ADRB2 5'-UTR甲基化作为哮喘严重程度和儿童NO 2相关性哮喘加重风险的生物标志物的潜在用途，并提供了重要环境与表观遗传关系的第一个证据。暴露与儿童哮喘的严重程度。

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