Different Gene Expressions of Alpha and Beta Glucocorticoid Receptors in Asthmatics

Document Type: Research article

Authors

1 Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

3 Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.

5 Tobacco Control Research Center, Iranian Anti-Tobacco Association, Tehran, Iran.

Abstract

The response to glucocorticoids (GCs) therapy classifies severe refractory asthma (SRA) and mild asthma, so the glucocorticoid receptors (GCRs) gene expression may be involved in SRA pathogenesis. Thus, it is aimed to compare the expression levels of two GCR isoforms (GCRα and GCRβ) in SRA, mild asthmatics, and healthy controls. Total RNA was isolated from the peripheral blood mononuclear lymphocytes of 13 SRA patients, 14 mild asthma patients and 30 healthy volunteers. The expression levels of GCR isoforms were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR).
The expression level of GCR isoforms did not show any significant difference between the cases/control groups. However, the relative expression analysis between asthma/control, SRA/control and SRA/asthma groups was in the order of 0.933, 0.768 and 0.823 for GCRα and 0.697, 1.014 and 1.454 for GCRβ, respectively. Also, the expression fold change of GCRα/GCRβ in asthma, SRA and control groups was 786.88, 445.72 and 588.13, respectively. The GCRα and GCRβ isoforms did not show any correlation in SRA; but they had significant correlation in both healthy volunteers (r = 0.490, P = 0.007) and mild asthmatics (r = 0.786, P = 0.001). Also, the GCRα expression level had significant inverse correlation with age in SRA (r = -0.709, P = 0.007).
Glucocorticoid receptors are related to, but not directly responsible for GC resistance. Since the GCRα/GCRβ expression ratio decreased in SRA, studies are needed to assess its value in diagnosing GC resistance.
 

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