Genetics and Epigenetic Regulation in Allergic Diseases

Abstract

Multiple mechanisms mediate the risk of allergic diseases, including altered innate and adaptive immune responses, gene-environment interactions, epigenetic regulation, and possibly gene-environment-epigene interactions. The gene-environment interaction adds to the complexity of allergy and asthma and is now being successfully explored using epigenetic approaches. Allergic diseases are inheritable, influenced by the environment, and modified by in utero exposures and aging; all of these features are also common to epigenetic regulation. Environmental exposures, including prenatal maternal smoking, have been associated with allergy-related outcomes that could be explained by epigenetic regulation. In addition, several allergy- and asthma-related genes have been found to be susceptible to epigenetic regulation, including genes important to T effector pathways (IFN-γ, IL-4, IL-13, IL-17) and T-regulatory pathways (FoxP3). Therefore, investigation into the relationship between epigenetic regulation and allergic disease is critical for understanding the development of allergy and asthma. Previously published experimental work, with few exceptions, has been comprised mostly of small observational studies and models in in vitro systems and animals. Recently, however, and due to new and advanced technologies, novel translational research and exciting and elegant experimental studies have been published. Epigenetic factors (DNA methylation, modifications of histone tails or noncoding RNAs) work with other components of the cellular regulatory machinery to control the levels of expressed genes. Technologies to investigate epigenetic factors on a genomic scale and comprehensive approaches to data analysis have recently emerged and continue to improve. This chapter addresses the fundamental questions of how genetics and epigenetics influence allergic diseases, including asthma. These include how anti-asthmatic agents can induce epigenetic changes, and how epigenetic regulation can influence cytokine and chemokine production in immune cells. The discovery and validation that genetic and epigenetic biomarkers may be linked to exposure, allergies, or both might lead to better genotyping and epigenotyping of the risk, prognosis, treatment prediction, and development of novel therapies for the treatment of allergy.