Impact of Gene Expression Associated with Glucocorticoid-Induced Transcript 1 (GLCCI1) on Severe Asthma and Future Exacerbation
| Autor: | Megumi Ueda, Eiji Nakatani, Keita Hirai, Toshihiro Shirai, Yuuka Rachi, Kunihiko Itoh, Sekiko Uehara |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Genotype Exacerbation NF-E2-Related Factor 2 Gene Expression Histone Deacetylase 2 Pharmaceutical Science Polymorphism Single Nucleotide Severity of Illness Index Peripheral blood mononuclear cell 03 medical and health sciences Receptors Glucocorticoid 0302 clinical medicine Adrenal Cortex Hormones Polymorphism (computer science) Administration Inhalation Gene expression Humans Medicine RNA Messenger Glucocorticoids Aged Asthma Pharmacology business.industry Hazard ratio General Medicine Middle Aged medicine.disease Pathophysiology respiratory tract diseases 030104 developmental biology ROC Curve Area Under Curve 030220 oncology & carcinogenesis Immunology Leukocytes Mononuclear Female business Glucocorticoid medicine.drug |
| Zdroj: | Biological and Pharmaceutical Bulletin. 42:1746-1752 |
| ISSN: | 1347-5215 0918-6158 |
| Popis: | Genetic variations in glucocorticoid-induced transcript 1 (GLCCI1) have been associated with the response to corticosteroid treatment. However, the associations of GLCCI1 polymorphisms or gene expression with the prognosis of asthma and pathophysiological factors related to steroid insensitivity remain unclear. We sought to investigate the associations of GLCCI1, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and histone deacetylase 2 (HDAC2) mRNA expression levels and the GLCCI1 rs37973 polymorphism with asthma severity and future exacerbation in patients with asthma. Subjects included 25 patients with severe asthma and 127 patients with nonsevere asthma. mRNA expression levels in peripheral blood mononuclear cells were measured and evaluated as predictors of severe asthma using receiver operating characteristic (ROC) analysis. The hazard ratios of the mRNA expression levels for time to first exacerbation in the 1-year follow-up period were calculated. GLCCI1, Nrf2, and HDAC2 mRNA expression levels were significantly lower in patients with severe asthma than in patients with nonsevere asthma and could predict severe asthma with an area under the ROC curve of 0.68, 0.71, and 0.65, respectively. In contrast, no relationship was found between the GLCCI1 rs37973 polymorphism and severe asthma. The hazard ratios for asthma exacerbation in patients with low GLCCI1, Nrf2, and HDAC2 mRNA expression levels were 3.24 (95% confidence interval, 1.42-7.40), 3.13 (1.37-7.16), and 2.98 (1.22-7.25), respectively. Patients with severe asthma could be distinguished by lower GLCCI1, Nrf2, and HDAC2 mRNA levels in peripheral blood cells, and all of these gene signatures could predict future asthma exacerbations. |
| Databáze: | OpenAIRE |
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