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Genetic and environmental interaction in allergy and asthma()()

Asthma is an inflammatory disorder of the airways involving coordinate up-regulation of T(H)2-type cytokines encoded in a cluster on chromosome 5q(31-33) on T cells and inflammatory cells. There is also a requirement for local airway susceptibility factors that, together with T(H)2 polarization, res...

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Detalles Bibliográficos
Autor principal: Holgate, Stephen T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mosby, Inc. 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172426/
https://www.ncbi.nlm.nih.gov/pubmed/10588993
http://dx.doi.org/10.1016/S0091-6749(99)70005-9
Descripción
Sumario:Asthma is an inflammatory disorder of the airways involving coordinate up-regulation of T(H)2-type cytokines encoded in a cluster on chromosome 5q(31-33) on T cells and inflammatory cells. There is also a requirement for local airway susceptibility factors that, together with T(H)2 polarization, results in hyperresponsiveness, variable airflow obstruction, and, over time, remodeling of the airway wall. Asthma has strong genetic and environmental components that interact both in the induction and subsequent expression of the disease phenotypes. Multiple genes are involved and probably interact. Whole genome screens are beginning to identify gene-rich regions of special relevance to asthma and atopy, although a novel disease-related gene has yet to be discovered from these. By contrast, there are a plethora of candidate genes whose function in relation to disease pathophysiologic mechanisms and response to treatment are known. Two examples are polymorphisms involving IL-4 receptors and the enzymes controlling cysteinyl leukotriene production. Abnormal signaling between the epithelium, which is in contact with the environment, and the underlying (myo)fibroblasts and dendritic cells indicating reactivation of the epithelial mesenchymal trophic unit, which is involved in fetal lung development and branching, provide a basis for asthma that encapsulates both T(H)2 polarization and airway wall remodeling. (J Allergy Clin Immunol 1999;104:1139-46.)