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Updated: Jun 18, 2026

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Published on: September 21, 2011
Clinical features associated with glucocorticoid receptor polymorphisms. An overview.
Laura Manenschijn1, Erica L T van den Akker, Steven W J Lamberts
1Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
Glucocorticoid receptor (GR) gene variations impact sensitivity to glucocorticoids (GCs), influencing metabolic health, longevity, and disease risk. These GR polymorphisms offer insights into personalized medicine for conditions like depression and cardiovascular disease.
Area of Science:
- Endocrinology
- Genetics
- Molecular Biology
Background:
- The glucocorticoid receptor (GR) mediates the effects of glucocorticoids (GCs), playing a vital role in physiological processes.
- Several GR gene polymorphisms are linked to variations in GC sensitivity, impacting health outcomes.
- Understanding these variants is crucial for comprehending individual responses to GCs and related diseases.
Purpose of the Study:
- To review and discuss the clinical relevance of specific glucocorticoid receptor (GR) gene polymorphisms.
- To explore the associations between GR variants (ER22/23EK, N363S, BclI, exon 9beta) and various health conditions.
- To highlight the implications of GR polymorphisms for GC sensitivity, metabolic health, and disease susceptibility.
Main Methods:
- Review of existing scientific literature on GR polymorphisms.
- Analysis of in vivo and in vitro experimental data.
- Correlation of genetic findings with clinical phenotypes and disease associations.
Main Results:
- The ER22/23EK polymorphism is associated with relative GC resistance, favorable metabolic conditions, longevity, and increased depression risk.
- The N363S and BclI polymorphisms are linked to enhanced GC sensitivity, with N363S associated with increased BMI and cardiovascular risk, while BclI is linked to abdominal fat and depression.
- The exon 9beta polymorphism leads to GC resistance via GR-beta, associated with inflammation, cardiovascular disease, and rheumatoid arthritis.
Conclusions:
- GR gene polymorphisms significantly influence GC sensitivity and are associated with a spectrum of clinical conditions, including metabolic disorders, cardiovascular disease, inflammatory conditions, and mental health disorders.
- These findings underscore the importance of considering genetic variations in GR when evaluating GC action and disease risk.
- Further research into GR variants may pave the way for personalized therapeutic strategies targeting the GC pathway.
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