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Glutathione S ‐transferase P1 Ile105Val polymorphism modulates allergen‐induced airway inflammation in human atopic asthmatics in vivo
Author(s) -
Hoskins A.,
Wu P.,
Reiss S.,
Dworski R.
Publication year - 2013
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12086
Subject(s) - immunology , in vivo , inflammation , allergen , glutathione s transferase , asthma , medicine , glutathione , allergy , biology , genetics , enzyme , biochemistry
Summary Background Glutathione S ‐transferase P1 is a Phase II cytoprotective and detoxifying enzyme that is widely expressed in human airways. The glutathione S ‐transferase P1 Ile105Val polymorphism has been linked with atopic disorders and asthma. Yet, little remains known about the regulation of allergic inflammation by glutathione S ‐transferase P1 in human asthmatics. Objective To establish the effect of the glutathione S ‐transferase P1 Ile105Val polymorphism on allergen‐induced airway inflammation and oxidant stress, and non‐specific bronchial hyperresponsiveness to methacholine and reactivity to specific allergen in mild human atopic asthmatics in vivo . Methods Five Val 105 /Val 105 , twelve Val 105 /Ile 105 and twenty Ile 105 /Ile 105 mild atopic asthmatics underwent methacholine challenge, inhaled allergen challenge and endobronchial allergen provocation through a bronchoscope. A panel of inflammatory cytokines and chemokines, F 2 ‐isoprostanes and isofuranes, markers of oxidative stress, thromboxane B 2 and immunoglobulin E were measured in bronchoalveolar lavage fluid at baseline and 24 h after allergen instillation. Results Asthmatics with glutathione S ‐transferase P1 Val 105 /Val 105 compared with asthmatics with the glutathione S ‐transferase P1 Val 105 /Ile 105 and Ile 105 /Ile 105 had greater generation of acute phase cytokines ( TNF ‐α, IL ‐6, CXCL 8), IL ‐12, CCL 11, thromboxane B 2 and immunoglobulin E at 24 h after local allergen challenge. The GSTP 1 genotype had no effect on airway hyperresponsiveness to methacholine and the reactivity to specific allergen. Conclusion The glutathione S ‐transferase P1 Ile105Val polymorphism markedly modifies allergen‐provoked airway inflammation in atopic asthmatics in vivo . Modulation of the biochemical milieu in response to allergen provides a mechanistic explanation for regulatory effects of glutathione S ‐transferase P1 polymorphism on airway pathophysiology, and may guide improvement of future therapeutic methods in human atopic asthmatics. These findings must me confirmed in a larger study population of asthmatics with various ethnicities.