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. Author manuscript; available in PMC: 2022 Feb 1.
Published in final edited form as: Pharmacol Ther. 2020 Sep 8;218:107674. doi: 10.1016/j.pharmthera.2020.107674

Table 1.

Summary of select findings from omics studies of glucocorticoid responses.

Omics Approach Select Findings
Genomics - A GLCCI1 SNP that was nominally associated with glucocorticoid response in patients treated with ICS, was in high linkage disequilibrium with a variant that was associated with decreased GLCCI1 expression in B cells (Tantisira, et al., 2011)
- No genome-wide significant variants were found in the largest GWAS of glucocorticoid response in asthma published to date based on subjects in clinical trials of fluticasone furoate and fluticasone propionate (Mosteller, et al., 2017)
- A CMTR1 SNP was associated with increased risk of asthma exacerbations in subjects from two Biobanks (Dahlin, et al., 2015)
- A locus in the intergenic region of APOBEC3B and APOBEC3C was associated with glucocorticoid responses in Hispanic/Latino and African American children (Hernandez-Pacheco, et al., 2019)
- Loci near GRIN3A and ACP1 were associated with increased risk of glucocorticoid-induced osteonecrosis in children with ALL (Karol, et al., 2015; Kawedia, et al., 2011).
Transcriptomics - Many glucocorticoid-responsive genes have been identified in primary airway epithelial and ASM cells, including TSC22D3, FKBP5, PER1, KLF15, DUSP1, CRISPLD2, CEBPD (Himes, et al., 2014; Kan, et al., 2019; Leigh, et al., 2016)
- Expression of the pro-apoptotic gene BIM was increased while the anti-apoptotic gene BCL2 was decreased with glucocorticoid exposure in ALL cells (Ploner, et al., 2008).
- Glucocorticoid-responsive genes in ALL cells include TXNIP, ZBTB16, PFKFB2 (Carlet, et al., 2010; Schmidt, et al., 2006; Tissing, et al., 2007)
Epigenomics - Some cell type-specific GR-binding sites lack a GRE and are enriched in open chromatin prior to glucocorticoid treatment (Gertz, et al., 2013).
- In A549 cells, GR-binding can occur through pre-established chromatin interactions that form a DNA loop. That is, some GRs that are bound to GREs also interact with distal enhancers at so-called GR-tethered binding sites (D’Ippolito, et al., 2018; Vockley, et al., 2016).
- GR and p65 cooperatively regulate transcription of anti-inflammatory genes (e.g. SERPINA1 and FOXP4) in BEAS-2B cells (Kadiyala, et al., 2016).
- PLCD1 was identified as a KLF15 target gene and a novel repressor of ASM hypertrophy (Sasse, et al., 2017).
Proteomics - Nasal fluid apoH was decreased in patients with allergic rhinitis after glucocorticoid treatment, especially among those who responded to glucocorticoids (H. Wang, Chavali, et al., 2011; H. Wang, Gottfries, et al., 2011)
- Serum VDBP had increased expression in patients with steroid-resistant asthma and its levels were highly correlated with proportions of neutrophils and monocytes (H. Jiang, et al., 2016).
- PCNA had decreased expression with glucocorticoid exposure in glucocorticoid-sensitive leukemia cell lines and was highly predictive of glucocorticoid response in children with ALL (N. Jiang, et al., 2011)
Metabolomics - Plasma metabolite changes in people following administration of oral dexamethasone reflected changes in pathways related to energy, lipolysis and muscle proteolysis, endogenous steroid production (Bordag, et al., 2015)