GR gene BclI polymorphysm changes the path, but not the level, of dexamethasone-induced cortisol suppression

Area of Science:

• Neuroendocrinology
• Genetics
• Psychiatry

Background:

• Hypothalamo-pituitary-adrenocortical (HPA) axis regulation involves cortisol binding to mineralocorticoid (MR) and glucocorticoid receptors (GR).
• HPA axis dysfunction is implicated in mental disorders like PTSD and depression.
• Dexamethasone suppression test (DST) findings vary, prompting investigation into influencing factors like GR gene polymorphisms.

Purpose of the Study:

• To investigate the influence of the glucocorticoid receptor (GR) gene BclI polymorphism on dexamethasone-induced cortisol suppression.
• To identify factors affecting DST outcomes in relation to GR gene variations.

Main Methods:

• 229 male subjects were genotyped for the GR gene BclI polymorphism (G and C alleles).
• Hierarchical linear regression analyzed dexamethasone-induced cortisol suppression as the dependent variable.
• The study examined interactions between allele counts and receptor variables to isolate G allele effects.

Main Results:

• Cortisol suppression levels were statistically similar across all BclI genotype groups.
• However, mineralocorticoid receptors (MRs) were found to be involved in the cortisol suppression mechanism exclusively in G allele carriers.

Conclusions:

• The study highlights a differential mechanism of cortisol suppression based on GR gene BclI polymorphism.
• Findings suggest that HPA axis-based therapies may need to be adjusted for G allele carriers.
• Limitations include a small number of CC carriers and unassessed MR functional properties.