Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 2001 N Soto Street, Mail Code 9237, Los Angeles, CA, 90033, USA,
Adv Exp Med Biol. 2014;795:183-99. doi: 10.1007/978-1-4614-8603-9_11.
Asthma is the most common chronic disease of childhood, and a growing body of evidence indicates that epigenetic variations may mediate the effects of environmental exposures on the development and natural history of asthma. Epigenetics is the study of mitotically or meiotically heritable changes in gene expression that occur without directly altering the DNA sequence. DNA methylation, histone modifications and microRNAs are major epigenetic variations in humans that are currently being investigated for asthma etiology and natural history. DNA methylation results from addition of a methyl group to the 5 position of a cytosine ring and occurs almost exclusively on a cytosine in a CpG dinucleotide. Histone modifications involve posttranslational modifications such as acetylation, methylation, phosphorylation and ubiquitination on the tails of core histones. MicroRNAs are short ~22 nucleotide long, non-coding, single-stranded RNAs that binds to complementary sequences in the target mRNAs, usually resulting in gene silencing. While many studies have documented relationships of environmental exposures that have been implicated in asthma etiology with epigenetic alterations, to date, few studies have directly linked epigenetic variations with asthma development. There are several methodological challenges in studying the epigenetics of asthma. In this chapter, the influence of epigenetic variations on asthma pathophysiology, methodological concerns in conducting epigenetic research and future direction of asthma epigenetics research are discussed.
哮喘是儿童最常见的慢性疾病，越来越多的证据表明，表观遗传变异可能介导环境暴露对哮喘的发生和自然史的影响。表观遗传学是研究有丝分裂或减数分裂中基因表达的可遗传变化，这些变化发生在不直接改变 DNA 序列的情况下。在人类中，DNA 甲基化、组蛋白修饰和 microRNAs 是主要的表观遗传变异，目前正在研究其在哮喘发病机制和自然史中的作用。DNA 甲基化是指在胞嘧啶环的 5 位上添加一个甲基基团，几乎只发生在 CpG 二核苷酸中的胞嘧啶上。组蛋白修饰涉及核心组蛋白尾部的翻译后修饰，如乙酰化、甲基化、磷酸化和泛素化。microRNAs 是长约 22 个核苷酸的非编码单链 RNA，与靶 mRNA 上的互补序列结合，通常导致基因沉默。虽然许多研究记录了与哮喘发病机制相关的环境暴露与表观遗传改变之间的关系，但迄今为止，很少有研究直接将表观遗传变异与哮喘的发生联系起来。在研究哮喘的表观遗传学方面存在一些方法学上的挑战。在本章中，讨论了表观遗传变异对哮喘病理生理学的影响、进行表观遗传研究的方法学关注点以及哮喘表观遗传学研究的未来方向。
