Heterogeneity in Asthma

Salam MT, Muhammad T. Salam, Salam, Muhammad T.

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.