Transcriptomics in tissue glucocorticoid sensitivity.
Adult
Alzheimer Disease
/ blood
Dexamethasone
/ pharmacology
Down-Regulation
/ drug effects
Female
Gene Expression Profiling
Glucocorticoids
/ pharmacology
Humans
Hydrocortisone
/ blood
Lupus Erythematosus, Systemic
/ blood
Male
Receptors, Glucocorticoid
/ genetics
Telomere Homeostasis
/ drug effects
Transcriptome
/ drug effects
Up-Regulation
/ drug effects
alpha-Synuclein
/ blood
RNA sequencing
glucocorticoid receptor
glucocorticoids
telomere length
tissue glucocorticoid sensitivity
transcriptomics
Journal
European journal of clinical investigation
ISSN: 1365-2362
Titre abrégé: Eur J Clin Invest
Pays: England
ID NLM: 0245331
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
04
10
2018
revised:
03
03
2019
accepted:
13
05
2019
pubmed:
16
5
2019
medline:
15
2
2020
entrez:
16
5
2019
Statut:
ppublish
Résumé
Synthetic glucocorticoids are widely used in the treatment of several inflammatory, autoimmune and lymphoproliferative disorders. However, considerable variation in response to therapeutic doses of glucocorticoids has been documented among individuals. The aim of our study was to identify novel glucocorticoid sensitivity-determining genes using genome-wide expression profiling in healthy subjects. One hundred one healthy subjects [mean age ± standard error of the mean (SEM); 26.52 ± 0.50 years] were given 0.25 mg dexamethasone at midnight, and serum cortisol concentrations were determined at 08:00 hours the following morning. Subjects were stratified into the 10% most glucocorticoid-sensitive and 10% most glucocorticoid-resistant according to the serum cortisol concentrations. Genomic DNA, RNA and plasma samples were obtained in the 22 subjects one month later. Transcriptomic analysis showed variability between glucocorticoid-resistant and glucocorticoid-sensitive subjects. One hundred thirty-three genes were upregulated and 49 downregulated in the glucocorticoid-resistant compared to the glucocorticoid-sensitive group. Further analysis revealed differences between 3 glucocorticoid-resistant and 3 glucocorticoid-sensitive subjects. The majority of the 1058 upregulated genes and 1139 downregulated genes were found to participate in telomere maintenance, systemic lupus erythematosus and Alzheimer's disease. Interestingly, Synuclein A, a key molecule in Parkinson's disease, was upregulated in the subgroup of glucocorticoid-sensitive subjects. We have identified differences in tissue sensitivity to glucocorticoids among healthy subjects at the transcriptomic level. These differences are associated with differential expression of genes related to autoimmune and neurological disorders.
Sections du résumé
BACKGROUND
BACKGROUND
Synthetic glucocorticoids are widely used in the treatment of several inflammatory, autoimmune and lymphoproliferative disorders. However, considerable variation in response to therapeutic doses of glucocorticoids has been documented among individuals. The aim of our study was to identify novel glucocorticoid sensitivity-determining genes using genome-wide expression profiling in healthy subjects.
METHODS
METHODS
One hundred one healthy subjects [mean age ± standard error of the mean (SEM); 26.52 ± 0.50 years] were given 0.25 mg dexamethasone at midnight, and serum cortisol concentrations were determined at 08:00 hours the following morning. Subjects were stratified into the 10% most glucocorticoid-sensitive and 10% most glucocorticoid-resistant according to the serum cortisol concentrations. Genomic DNA, RNA and plasma samples were obtained in the 22 subjects one month later.
RESULTS
RESULTS
Transcriptomic analysis showed variability between glucocorticoid-resistant and glucocorticoid-sensitive subjects. One hundred thirty-three genes were upregulated and 49 downregulated in the glucocorticoid-resistant compared to the glucocorticoid-sensitive group. Further analysis revealed differences between 3 glucocorticoid-resistant and 3 glucocorticoid-sensitive subjects. The majority of the 1058 upregulated genes and 1139 downregulated genes were found to participate in telomere maintenance, systemic lupus erythematosus and Alzheimer's disease. Interestingly, Synuclein A, a key molecule in Parkinson's disease, was upregulated in the subgroup of glucocorticoid-sensitive subjects.
CONCLUSIONS
CONCLUSIONS
We have identified differences in tissue sensitivity to glucocorticoids among healthy subjects at the transcriptomic level. These differences are associated with differential expression of genes related to autoimmune and neurological disorders.
Substances chimiques
Glucocorticoids
0
NR3C1 protein, human
0
Receptors, Glucocorticoid
0
SNCA protein, human
0
alpha-Synuclein
0
Dexamethasone
7S5I7G3JQL
Hydrocortisone
WI4X0X7BPJ
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13129Informations de copyright
© 2019 Stichting European Society for Clinical Investigation Journal Foundation.