Beyond genetic variants in allergic asthma: DNA methylation

Published Online: October 13, 2016

Asthma continues to disproportionately affect underrepresented minorities in the United States (US), especially African Americans who have more severe asthma and a poorer response to therapy. Allergic asthma is a heritable disease that is strongly influenced by environmental exposures, largely allergens but also air pollution and cigarette smoke, among others. Genetic studies performed to date have only been able to explain a small portion of disease heritability. Epigenetics, meaning ‘above genetics’, is the study of epigenetic marks, that are modifications of DNA and proteins associated with DNA that allow DNA to be accessible so that gene transcription can occur. These are not changes to DNA or protein sequence but epigenetic marks are important in regulating how much of each gene is expressed in the cell. The most commonly studied of these epigenetic marks is DNA methylation that may be influenced by exposures that can be important in allergic asthma.

In a research article published in The Journal of Allergy & Clinical Immunology (JACI), Yang and colleagues  searched for DNA methylation changes throughout the human genome that are associated with allergic asthma in African American children living in inner cities in the US. This study was performed as a part of the Inner City Asthma Consortium sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). DNA methylation was examined in nasal epithelial cells, because these cells are constantly exposed to the environment and have been previously shown to have the same asthma-associated gene expression changes as lung epithelial cells.

Researchers found hundreds of DNA methylation changes throughout the genome that are associated with allergic asthma in inner city African American children. These DNA methylation changes also affect expression levels of genes already known to be important in allergic asthma. Identified DNA methylation changes are large in magnitude, which is supportive of their critical role in regulating gene expression in the respiratory epithelium of allergic asthmatics. The most likely cause of these DNA methylation changes are environmental exposures. While this study did not have the data needed to examine the relationship of exposures and epigenetics, the investigators plan to address this issue in their future work.

This study is important because it is the first one to report large DNA methylation changes in the respiratory epithelium of allergic asthmatic children. Identification of key epigenetic marks that are shaped by the environment and influence expression of specific genes will not only help us have a better understanding of etiology, heterogeneity and severity of asthma but also empower us to develop biologically driven biomarkers for secondary prevention of this disease.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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