[Nucleotide sequence variants of the glucocorticoid receptor gene and their significance in determining...

Nucleotide sequence variants of the glucocorticoid receptor gene and their significance in determining glucocorticoid sensitivity. The physiologic response and sensitivity to glucocorticoids may significantly differ among species, individuals, tissues and cell types. The variability of the effect of endogenous and exogenous glucocorticoids is largely determined by genetic components, of which the authors review the knowledge on the glucocorticoid receptor gene. The authors describe the genomic and non-genomic pathways of receptor function, the significance of isoforms produced during receptor protein formation, the pathomechanism of glucocorticoid resistance syndrome and the results of clinical investigations related to receptor gene polymorphisms. Through subtle alteration of receptor function, the gene polymorphisms may increase or diminish sensitivity to glucocorticoids and may play a role in the pathogenesis of metabolic disorders. In their own studies the authors found, that the N363S polymorphism, which increases glucocorticoid sensitivity, may play a role in the pathogenesis of bilateral adrenal adenomas, it may modify the clinical phenotype of patients with congenital adrenal hyperplasia, and may have an impact on steroid-induced ocular hypertension. It is presumed that further research in other diseases will continue to complete our knowledge on the pathophysiology of glucocorticoid receptor gene polymorphisms.