Early origins of asthma (and allergy)

Abstract

Asthma is the most common chronic disease starting in childhood and persisting into adulthood in many cases. During childhood, different forms of asthma and wheezing disorders exist that can be discriminated by the mechanisms they are caused by. Specific genetic constellations and exposure against environmental factors during early childhood and in utero play a decisive role in the early development of the disease. Epigenetic mechanisms which are master regulators of gene transcription and thus govern the accessibility and use of genome information, have recently been identified as a "third power" determining many features in the early development of asthma and allergy.

Keywords: Asthma; Epigenetics; Gene by environment; Interaction; Wheezing.

Fig. 1

Course of wheeze prevalences in latent class analysis (LCA) and clinical phenotypes. a Prevalences of current wheeze (i.e., in the last 12 months) in the first 6 years of life are shown for the five class solution of the LCA. b Wheeze prevalences in the first 6 years of life stratified for clinical phenotypes as defined in the text and reference [2], used with permission

Fig. 2

Epigenetic mechanisms in humans. The genome has a three-dimensional structure. The DNA is configured as an alpha helix of nucleotides. (1) The addition of methyl groups to cytosines changes the configuration of the helix and hinders the transcription machinery to attach to DNA. The DNA is further organized in nucleosomes which contain 146 basepairs of DNA and eight histone proteins (4 × 2 histone proteins). (2) Modification of histones by methylation or acetylation changes the accessibility of DNA at the site of these nucleosomes. Once mRNA is produced, (3) interfering mi-RNA can regulate transcription efficiency before translation into protein can occur (adapted from figure 7.6, chapter on genetics by Michael Kabesch in Pädiatrische Pneumologie, Editors Erika von Mutius et al., Springer, ISBN 978-3-642-34827-3)