Genetics of allergy and asthma.

LEARNING
OBJECTIVES: This article summarizes the latest information regarding the role of genetic influences in the development of allergic disorders and asthma and reviews our current information on some of the most likely genes responsible for these conditions. After reading this article, the reader will have a better understanding of the current molecular biologic techniques that are being used to understand complex genetic disorders such as allergies and asthma. The reader should understand the value of how this genetic insight will lead to the recognition of the presence of specific subtypes of these disorders that require unique therapeutic interventions. This information can also be used to identify genetically at risk children and thereby offer earlier intervention. Finally, understanding the genetic causes of allergies and asthma will lead to the development of the next--hopefully curative--generation of asthma and allergy therapeutics. DATA SOURCES: A detailed literature search was conducted. Studies considered relevant, well performed, and appropriately controlled were used. Only human studies are included and only the English language literature was reviewed. Some of the information presented is based on the author's own research experience. STUDY SELECTION: Material was only taken from peer-reviewed journals and appropriate reviews. RESULTS AND
CONCLUSIONS: Asthma and allergic diseases are examples of disorders having an unmistakable genetic predisposition, but in the absence of a classic Mendelian inheritance pattern. These "complex" genetic disorders are caused by the interactions of multiple interacting genes some having protective value and some contributing to disease development and with each gene having its own variable tendency to be expressed. In addition, these disorders require the presence of appropriate environmental triggers for their expression. One approach to identifying the genetic basis for these conditions is to perform a genome-wide search in which the location of the disease-causing gene on a human chromosome is identified and nearby genes that may be responsible are subsequently identified. An alternative approach to identifying heritable components to asthma and allergy is to evaluate disordered structure or regulation within genes known to be involved in these disorders. Using these approaches, studies have suggested that genes within the cytokine gene cluster on chromosome 5 (including interleukins-3, -4, -5, -9, and -13), chromosome 11 (the beta chain of the high affinity IgE receptor), chromosome 16 (the IL-4 receptor), and chromosome 12 (stem cell factor, interferon-gamma, insulin growth factor, and Stat 6 [IL-4 Stat]) may contribute to asthma and allergy development. In addition, data support involvement of genes involved in antigen-presentation (MHC class II genes) and T cell responses (the T cell receptor alpha chain). Finally, disease-contributing alleles may be present on genes for the beta-adrenergic receptor, 5-lipoxygenase, and leukotriene C4 synthase.