Published ahead of print on January 10, 2008, doi:10.1164/rccm.200710-1511PP
Am. J. Respir. Crit. Care Med., Volume 177, Number 6, March 2008, 567-573
A more recent version of this article appeared on March 15, 2008
Submitted on October 12, 2007
Accepted on January 10, 2008
Environmental Epigenetics and Asthma: Current Concepts and Call for Studies
Rachel L Miller1* and Shuk-mei Ho2
1 Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA,
2 Department of Environmental Health and Cancer Center, University of Cincinnati, College of Medicine, Cincinnati, OH, USA
* To whom correspondence should be addressed. E-mail: rlm14{at}columbia.edu.
Objective: Recent studies suggest that epigenetic regulation (heritable changes in gene expression that occur in the absence of alterations in DNA sequences) may in part mediate the complex gene-by-environment interactions that can lead to asthma. The variable natural history of asthma (i.e. incidence and remission of symptoms) may be a result of epigenetic changes such
as DNA methylation, covalent histone modifications, microRNA changes and chromatin alterations following early or later environmental exposures.
Results: Findings from multiple epidemiological and experimental studies indicate that asthma risk may be modified by epigenetic regulation. One study suggested that the transmission of asthma risk may occur across multiple generations. Experimental studies provide substantial in vitro data indicating that DNA methylation of genes critical to T helper cell differentiation may induce polarization towards or away from an allergic phenotype.
Conclusion: Despite this initial progress, fundamental questions remain that need to be addressed by well-designed research studies. Data generated from controlled experiments using in vivo models and/or clinical specimens collected following environmental exposure monitoring are limited. Importantly, cohort driven epigenetic research has the potential to address key questions, such as those concerning the influence of timing of exposure, dose of exposure, diet, and ethnicity on susceptibility to asthma development. There is immense promise that the study of environmental epigenetics will help us understand a theoretically preventable environmental disease.
Key words: Epigenetics, asthma risk, DNA methylation, histone code, microRNA
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