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TBX21: a functional variant predicts improvement in asthma with the use of inhaled corticosteroids

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Please use this identifier to cite or link to this item: http://hdl.handle.net/1928/1922

TBX21: a functional variant predicts improvement in asthma with the use of inhaled corticosteroids

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Title: TBX21: a functional variant predicts improvement in asthma with the use of inhaled corticosteroids
Author: Tantisira, KG; Hwang, ES; Raby, BA; Silverman, ES; Lake, SL; Richter, BG; Peng, SL; Drazen, JM; Glimcher, LH; Weiss, ST; Raby, BA; Silverman, ES; Lake, SL; Richter, BG; Peng, SL; Drazen, JM; Glimcher, LH; Weiss, ST
Subject(s): TBX21
functional variant
asthma
inhaled corticosteroids
Abstract: TBX21 encodes for the transcription factor T-bet (T-box expressed in T cells), which influences naive T lymphocyte development and has been implicated in asthma pathogenesis. Specifically, the T-bet knockout mouse spontaneously develops airway hyperresponsiveness and other changes consistent with asthma. Because airway responsiveness is moderated by the use of inhaled corticosteroids in asthma, it is conceivable that genetic variation in TBX21 may alter asthma phenotypes in a treatment-specific fashion. Here we demonstrate that the nonsynonymous variation in TBX21 coding for replacement of histidine 33 with glutamine is associated with significant improvement in the PC(20) (a measure of airway responsiveness) of asthmatic children in a large clinical trial spanning 4 years. We note that this increase occurs only in the children randomized to inhaled corticosteroids and that it dramatically enhances the overall improvement in PC(20) associated with inhaled corticosteroid usage. The average PC(20) at trial end for subjects on inhaled corticosteroids possessing a variant allele was in the normal range for nonasthmatics. In cellular models, we show that the TBX21 variant increases T helper 1 and decreases T helper 2 cytokine expression comparably with wild type. TBX21 may thus be an important determinant pharmacogenetic response to the therapy of asthma with inhaled corticosteroids.
Date: 2006-09-20
Publisher: Tantisira, KG - Proceedings of the National Academy of Sciences of the United States of A
Citation: 2004 Dec 28;101(52):18099-104. Epub 2004 Dec 16
Description: For full-test go to PubMed ID: 15604153
URI: http://hdl.handle.net/1928/1922

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