Genetic and environmental interaction in allergy and asthma

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Presentation transcript:

Genetic and environmental interaction in allergy and asthma Stephen T. Holgate, BSc, MD, DSc, FRCP, FRCPath, FMed, Sci Journal of Allergy and Clinical Immunology Volume 104, Issue 6, Pages 1139-1146 (December 1999) DOI: 10.1016/S0091-6749(99)70005-9 Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig. 1 Eigenvector plot shows relationship between various clinical phenotypes and the summated scores for asthma and atopy derived by principal-component regression analysis. Journal of Allergy and Clinical Immunology 1999 104, 1139-1146DOI: (10.1016/S0091-6749(99)70005-9) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig. 2 Different approaches to identify susceptibility genes: random genome search with microsatellite markers (upper), microsatellite markers close to a known gene (lower left), and mutation analysis of known gene or its promoter (lower right). Journal of Allergy and Clinical Immunology 1999 104, 1139-1146DOI: (10.1016/S0091-6749(99)70005-9) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig. 3 IL-4 activates a number of signaling pathways, including signal transduction and activators of transcription (STAT) 6 and IRS (insulin receptor substrate) 1 through IL-4 receptor (IL-4R). IL-4R is composed of α chain (IL-4Rα) and γ (γc) α chain; however, other forms do exist because of formation of heterogeneous structures with a component of α γ chain, which is shared with the IL-2r IL-13 receptor (IL-13α1) Signal transduction through IL-4R is thought to involve activation of IRS1/2 and STAT6, which leads to cell proliferation and activation of gene transcription. A number of polymorphisms have been identified within the IL-4Rα gene and several of these result in amino acid coding changes. Several of these polymorphisms have been shown to have effects on IL4 signal transduction. However, the precise effects of each polymorphism and combinations of these polymorphisms are still unclear. Journal of Allergy and Clinical Immunology 1999 104, 1139-1146DOI: (10.1016/S0091-6749(99)70005-9) Copyright © 1999 Mosby, Inc. Terms and Conditions