Identification of a key gene module associated with glucocorticoid- induced derangement in bone mineral density in patients with asthma

• Published in: Scientific reports Vol. 9; no. 1; pp. 20133 - 10
• Main Authors: Lee, Suh-Young, Won, Ha-Kyeong, Kim, Byung-Keun, Kim, Sae-Hoon, Chang, Yoon-Seok, Cho, Sang-Heon, Kelly, H William, Tantisira, Kelan G, Park, Heung-Woo
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 27.12.2019; Nature Publishing Group UK
• Subjects: Adolescent; Aged; Anti-Asthmatic Agents - adverse effects; Anti-Asthmatic Agents - therapeutic use; Asthma; Asthma - complications; Asthma - drug therapy; Asthma - genetics; Biomarkers; Bone density; Bone Density - genetics; Bone mineral density; Child; Children; Computational Biology - methods; Female; Gene expression; Gene Expression Profiling; Gene Regulatory Networks; Genetic Predisposition to Disease; Genome-Wide Association Study; Glucocorticoids; Glucocorticoids - adverse effects; Glucocorticoids - therapeutic use; Humans; Leukocytes (mononuclear); Literature reviews; Lymphocytes B; Male; Metabolic pathways; Middle Aged; Osteoporosis - diagnostic imaging; Osteoporosis - etiology; Osteoporosis - metabolism; Osteoporosis - pathology; Peripheral blood mononuclear cells; Transcriptome
• DOI: 10.1038/s41598-019-56656-9
• ISSN: 2045-2322

Derangement in bone mineral density (BMD) caused by glucocorticoid is well-known. The present study aimed to find key biological pathways associated with low BMD after glucocorticoid treatment in asthmatics using gene expression profiles of peripheral blood cells. We utilized immortalized B cells (IBCs) from 32 childhood asthmatics after multiple oral glucocorticoid bursts and peripheral blood mononuclear cells (PBMCs) from 17 adult asthmatics after a long-term use of oral glucocorticoid. We searched co-expressed gene modules significantly related with the BMD Z score in childhood asthmatics and tested if these gene modules were preserved and significantly associated with the BMD Z score in adult asthmatics as well. We identified a gene module composed of 199 genes significantly associated with low BMD in both childhood and adult asthmatics. The structure of this module was preserved across gene expression profiles. We found that the cellular metabolic pathway was significantly enriched in this module. Among 18 hub genes in this module, we postulated that 2 genes, CREBBP and EP300, contributed to low BMD following a literature review. A novel biologic pathway identified in this study highlighted a gene module and several genes as playing possible roles in the pathogenesis of glucocorticoid- induced derangement in BMD.