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Transcriptomics in tissue glucocorticoid sensitivity.

Nicolas C Nicolaides1,2, Alexandros Polyzos3, Eleni Koniari1

  • 1Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, University of Athens Medical School, "Aghia Sophia" Children's Hospital, Athens, Greece.

European Journal of Clinical Investigation
|May 16, 2019
PubMed
Summary

Individual differences in glucocorticoid sensitivity exist at the genetic level. This study identified gene expression variations linked to autoimmune and neurological conditions in healthy subjects.

Keywords:
RNA sequencingglucocorticoid receptorglucocorticoidstelomere lengthtissue glucocorticoid sensitivitytranscriptomics

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Area of Science:

  • Pharmacogenomics
  • Molecular biology
  • Human genetics

Background:

  • Synthetic glucocorticoids are vital for treating inflammatory and autoimmune diseases.
  • Significant inter-individual variability exists in patient responses to glucocorticoid therapy.
  • Identifying genetic determinants of glucocorticoid sensitivity is crucial for personalized medicine.

Purpose of the Study:

  • To discover novel genes influencing glucocorticoid sensitivity.
  • To investigate genome-wide gene expression profiles in healthy individuals with varying glucocorticoid responses.

Main Methods:

  • 101 healthy subjects received dexamethasone (0.25 mg).
  • Serum cortisol levels were measured to stratify subjects into highly sensitive and resistant groups.
  • Genome-wide transcriptomic analysis was performed on selected subjects.

Main Results:

  • Significant transcriptomic differences were observed between glucocorticoid-sensitive and resistant groups.
  • Gene expression patterns associated with telomere maintenance, systemic lupus erythematosus, and Alzheimer's disease were identified.
  • Upregulation of Synuclein A, linked to Parkinson's disease, was noted in glucocorticoid-sensitive individuals.

Conclusions:

  • Tissue sensitivity to glucocorticoids varies among healthy individuals at the transcriptomic level.
  • These variations correlate with the differential expression of genes implicated in autoimmune and neurological disorders.
  • Findings suggest a genetic basis for glucocorticoid response variability, potentially impacting treatment strategies.