Transcriptomics in tissue glucocorticoid sensitivity.
Level 4 - case-series / case-control
Observational extreme-phenotype cohort study evaluating transcriptomic profiles
PubMed 31091335 · doi:10.1111/eci.13129
What was done
A cohort of 101 healthy subjects (mean age 26.52 ± 0.50 years) underwent a 0.25 mg midnight dexamethasone suppression test with serum cortisol measured at 08:00 the following morning. Participants in the top 10% most glucocorticoid-sensitive and top 10% most glucocorticoid-resistant groups (n = 22 total) underwent genome-wide expression profiling from blood samples collected one month later.
What was found
Transcriptomic profiling identified 133 upregulated and 49 downregulated genes in glucocorticoid-resistant compared to glucocorticoid-sensitive subjects. A secondary analysis in a subset of 3 resistant versus 3 sensitive subjects identified 1,058 upregulated and 1,139 downregulated genes enriched for telomere maintenance, systemic lupus erythematosus, and Alzheimer's disease pathways, as well as upregulation of Synuclein A in sensitive subjects. Quantitative effect sizes and statistical significance thresholds were not reported in the abstract.
Why it matters
These findings suggest that baseline tissue sensitivity to glucocorticoids in healthy people correlates with distinct transcriptomic patterns, offering candidate genes that may explain inter-individual variability in glucocorticoid responsiveness.
Limits
The primary transcriptomic analysis was restricted to an extreme-phenotype sample of 22 subjects, with deeper pathway analysis narrowed to only 6 individuals. The study was conducted in healthy young volunteers and lacks functional validation, replication in an independent cohort, or assessment of response in clinical disease states.
Cited by
- context Cortisol alters the expression of approximately 25% of the human genome, including many genes involved in inflammation.