TY - JOUR
T1 - Polymorphisms of the glucocorticoid receptor gene and adrenal suppression in patients with chronic obstructive pulmonary disease treated with glucocorticoids for acute exacerbations
AU - Sivapalan, Pradeesh
AU - Borresen, Stina W
AU - Eklöf, Josefin
AU - Klose, Marianne
AU - Holm, Freja S
AU - Feldt-Rasmussen, Ulla
AU - Rossing, Maria
AU - Jørgensen, Niklas R.
AU - Marvig, Rasmus L.
AU - Saeed, Mohamad Isam
AU - Wilcke, Jon Torgny
AU - Seersholm, Niels
AU - Mathioudakis, Alexander G.
AU - Vestbo, Jorgen
AU - Jensen, Jens Ulrik Stæhr
PY - 2022/1/24
Y1 - 2022/1/24
N2 - Background: Single-nucleotide polymorphisms (SNPs) of the glucocorticoid receptor (GR) gene NR3C1 modulate sensitivity to glucocorticoids (GC), thus may and thus may affect the therapeutic effects of GCs. We investigated the prevalence of adrenal suppression after treatment with GCs and evaluated whether high GC-sensitivity haplotypes were associated with an increased risk of adrenal suppression and metabolic disorders in patients with chronic obstructive pulmonary disease (COPD). Methods: In an observational prospective cohort study, we recruited 50 patients with severe COPD between 2017 and 2019 who were treated for five days with GCs. All patients were genotyped for BclI, N363S, ER22/23EK and 9β SNPs. Results: The prevalence of adrenal suppression (corticotropin-stimulated plasma-cortisol ≤ 420 nmol/L) 1 month after GC treatment was 5% for the whole cohort. SNP frequency was: N363S 3.9%, Bcl1 63.2%, ER22/23EK 2.6% and 9β 18.4%. There was no correlation between high-sensitivity (p-value 0.79) or low-sensitivity (p-value 0.26) GR polymorphism and stimulated cortisol levels. There was no difference between adrenal suppression and metabolic disorders in COPD patients stratified for high vs. low GC-sensitivity GR haplotypes plus wild type (p-value > 0.05). Conclusions: The BclI and N363S polymorphisms do not seem to increase the risk of adrenal suppression or metabolic disorders in adults treated with corticosteroids for COPD exacerbations.
AB - Background: Single-nucleotide polymorphisms (SNPs) of the glucocorticoid receptor (GR) gene NR3C1 modulate sensitivity to glucocorticoids (GC), thus may and thus may affect the therapeutic effects of GCs. We investigated the prevalence of adrenal suppression after treatment with GCs and evaluated whether high GC-sensitivity haplotypes were associated with an increased risk of adrenal suppression and metabolic disorders in patients with chronic obstructive pulmonary disease (COPD). Methods: In an observational prospective cohort study, we recruited 50 patients with severe COPD between 2017 and 2019 who were treated for five days with GCs. All patients were genotyped for BclI, N363S, ER22/23EK and 9β SNPs. Results: The prevalence of adrenal suppression (corticotropin-stimulated plasma-cortisol ≤ 420 nmol/L) 1 month after GC treatment was 5% for the whole cohort. SNP frequency was: N363S 3.9%, Bcl1 63.2%, ER22/23EK 2.6% and 9β 18.4%. There was no correlation between high-sensitivity (p-value 0.79) or low-sensitivity (p-value 0.26) GR polymorphism and stimulated cortisol levels. There was no difference between adrenal suppression and metabolic disorders in COPD patients stratified for high vs. low GC-sensitivity GR haplotypes plus wild type (p-value > 0.05). Conclusions: The BclI and N363S polymorphisms do not seem to increase the risk of adrenal suppression or metabolic disorders in adults treated with corticosteroids for COPD exacerbations.
M3 - Article
SN - 1932-6203
JO - PL o S One
JF - PL o S One
ER -