Glutathione S-transferase P1 Ile105Val polymorphism modulates allergen-induced airway inflammation in human atopic asthmatics in vivo

• Published in: Clinical and experimental allergy Vol. 43; no. 5; pp. 527 - 534
• Main Authors: Hoskins, A., Wu, P., Reiss, S., Dworski, R.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.05.2013; Wiley Subscription Services, Inc
• Subjects: Adult; allergen challenge; Allergens - immunology; allergic inflammation; Asthma - genetics; Asthma - immunology; Asthma - metabolism; atopic asthma; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - metabolism; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Female; glutathione S-transferase P1; Glutathione S-Transferase pi - genetics; Humans; Hypersensitivity, Immediate - genetics; Hypersensitivity, Immediate - immunology; Hypersensitivity, Immediate - metabolism; Ile105Val polymorphism; Immunoglobulin E - immunology; Inflammation Mediators - immunology; Inflammation Mediators - metabolism; Male; methacholine challenge; Middle Aged; oxidant stress; Oxidative Stress; Polymorphism, Genetic; Young Adult
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/cea.12086

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 Val105/Val105, twelve Val105/Ile105 and twenty Ile105/Ile105 mild atopic asthmatics underwent methacholine challenge, inhaled allergen challenge and endobronchial allergen provocation through a bronchoscope. A panel of inflammatory cytokines and chemokines, F2‐isoprostanes and isofuranes, markers of oxidative stress, thromboxane B2 and immunoglobulin E were measured in bronchoalveolar lavage fluid at baseline and 24 h after allergen instillation. Results Asthmatics with glutathione S‐transferase P1 Val105/Val105 compared with asthmatics with the glutathione S‐transferase P1 Val105/Ile105 and Ile105/Ile105 had greater generation of acute phase cytokines (TNF‐α, IL‐6, CXCL8), IL‐12, CCL11, thromboxane B2 and immunoglobulin E at 24 h after local allergen challenge. The GSTP1 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.