Analysis of the Ser786Pro interleukin-4 receptor alpha allelic variant in allergic and nonallergic asthma and its functional consequences

Bibliographische Detailangaben
Veröffentlicht in:	Clinical immunology (Orlando, Fla.). - 1999. - 100(2001), 3 vom: 01. Sept., Seite 298-304
1. Verfasser:	Andrews, R P (VerfasserIn)
Weitere Verfasser:	Burrell, L, Rosa-Rosa, L, Cunningham, C M, Brzezinski, J L, Bernstein, J A, Khurana Hershey, G K
Format:	Aufsatz
Sprache:	English
Veröffentlicht:	2001
Zugriff auf das übergeordnete Werk:	Clinical immunology (Orlando, Fla.)
Schlagworte:	Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Intracellular Signaling Peptides and Proteins Receptors, Interleukin-4 STAT6 Transcription Factor STAT6 protein, human Trans-Activators Interleukin-4 207137-56-2 mehr... PTPN6 protein, human EC 3.1.3.48 Protein Tyrosine Phosphatase, Non-Receptor Type 6 Protein Tyrosine Phosphatases Ptpn6 protein, mouse

Beschreibung
Zusammenfassung:	Copyright 2001 Academic Press. Asthma and other atopic disorders affect a large percentage of the population. While many factors contribute to the phenotype of asthma, there is a strong genetic predisposition. IL-4 is a central mediator of allergic inflammation. Along with IL-13, it is the major cytokine responsible for the induction of IgE synthesis. Furthermore, IL-4 acts on Th0 cells and promotes their differentiation into Th2 cells resulting in the production of more IL-4 and IL-13, thereby propagating the allergic cascade. Both IL-4 and IL-13 utilize IL-4Ralpha as a component of their cognate receptor complexes. Eight polymorphisms of the IL-4Ralpha gene resulting in amino acid changes in the coding sequence have been described, and several have been associated with asthma. The central objective of this study was to elucidate the role of the Ser786Pro polymorphism in asthma and its impact on IL-4R function. One-hundred ninety-six individuals with asthma and 53 controls were genotyped for Pro786. Pro786 occurred infrequently in the general population with an allele frequency of 1.8% and, thus, is unlikely to play a major role in atopy or asthma. The Pro786 allele frequency was 1.5% in the asthma group and 2.8% in the control group. The asthma group was subdivided into allergic and nonallergic asthma, and the Pro786 allele frequencies were 1.7 and 1.0%, respectively. The data suggested linkage disequilibrium between Ser786Pro and the Gln576Arg allele, which is associated with atopy. In order to study the impact of the polymorphism on receptor signaling function, we transfected a mouse B lymphoma cell line with the wild-type and Pro786 variants of human IL-4Ralpha. The Ser786Pro polymorphism in isolation did not affect IL-4R function
Beschreibung:	Date Completed 20.09.2001 Date Revised 15.11.2007 published: Print Citation Status MEDLINE
ISSN:	1521-7035