Epigenetics of human asthma and allergy: promises to keep.
OBJECTIVE
The interest in asthma epigenetics is high because epigenetic mechanisms likely contribute to the environmental origins of the disease and its phenotypic variability. This review presents the main findings of asthma epigenetics and the challenges that still delay progress.


METHODS
We examined the current literature on asthma epigenetics (31 reviews and 25 original data publications).


METHODS
We focused on DNA methylation studies in populations.


RESULTS
Both genome-wide and candidate gene studies have explored DNA methylation in allergic disease. Genome-wide studies ask whether and which regions of the genome are differentially methylated in relation to the phenotype of interest. Identification of such regions provides clues about the identity of the genes, pathways and networks underpinning a phenotype and connects these networks to the phenotype through epigenetic mechanisms. Candidate gene studies examine DNA methylation in genes chosen because of their known or hypothesized role in immunity, responses to environmental stimuli or disease pathogenesis. Most existing studies in asthma and allergy focused on candidate genes involved in the response to environmental pollutants.


CONCLUSIONS
Asthma epigenetics is still in its infancy. The paucity of primary literature originates from methodological and analytical challenges of genome-wide studies, the difficulties in interpreting small differences in DNA methylation, and the need to develop robust bioinformatic tools for pathway, network and system analyses of epigenetic data. Once these challenges have been overcome, epigenetic studies will likely provide important insights about the inception and pathogenesis of allergic disease and will help define disease endotypes.
Functional Genomics Laboratory, Arizona Respiratory Center; Arizona Center for the Biology of Complex Diseases; Department of Cellular and Molecular Medicine; and The Bio5 Institute, University of Arizona, Tucson, Arizona, USA.
Avery
A
Devries
Donata
D
Vercelli
D001249:Asthma / Q000209:etiology / Q000276:immunology*; D019175:DNA Methylation / Q000276:immunology*; D004781:Environmental Exposure / Q000009:adverse effects*; D044127:Epigenesis, Genetic / Q000276:immunology*; D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study; D006801:Humans