Airways Disease Section, National Heart & Lung Institute, Imperial College, Dovehouse Street, London, SW3 6LY, UK.
Epigenomics. 2010 Aug;2(4):523-37. doi: 10.2217/epi.10.27.
Asthma is a chronic inflammatory disease of the airways. The causes of asthma and other inflammatory lung diseases are thought to be both environmental and heritable. Genetic studies do not adequately explain the heritability and susceptabilty to the disease, and recent evidence suggests that epigentic changes may underlie these processes. Epigenetics are heritable noncoding changes to DNA and can be influenced by environmental factors such as smoking and traffic pollution, which can cause genome-wide and gene-specific changes in DNA methylation. In addition, alterations in histone acetyltransferase/deacetylase activities can be observed in the cells of patients with lung diseases such as severe asthma and chronic obstructive pulmonary disease, and are often linked to smoking. Drugs such as glucocorticoids, which are used to control inflammation, are dependent on histone deacetylase activity, which may be important in patients with severe asthma and chronic obstructive pulmonary disease who do not respond well to glucocorticoid therapy. Future work targeting specific histone acetyltransferases/deacetylases or (de)methylases may prove to be effective future anti-inflammatory treatments for patients with treatment-unresponsive asthma.
哮喘是一种气道慢性炎症性疾病。哮喘和其他肺部炎症性疾病的病因被认为既有环境因素，也有遗传因素。遗传研究不能充分解释疾病的遗传性和易感性，最近的证据表明，表观遗传变化可能是这些过程的基础。表观遗传是指 DNA 的可遗传的非编码变化，可受环境因素（如吸烟和交通污染）的影响，这些因素会导致 DNA 甲基化的全基因组和基因特异性变化。此外，在患有严重哮喘和慢性阻塞性肺疾病等肺部疾病的患者的细胞中可以观察到组蛋白乙酰转移酶/去乙酰化酶活性的改变，这些改变通常与吸烟有关。用于控制炎症的药物，如糖皮质激素，依赖于组蛋白去乙酰化酶的活性，这在对糖皮质激素治疗反应不佳的严重哮喘和慢性阻塞性肺疾病患者中可能很重要。针对特定组蛋白乙酰转移酶/去乙酰化酶或（去）甲基化酶的未来研究可能会为治疗反应不佳的哮喘患者提供有效的抗炎治疗方法。
