A Polymorphism in the Glucocorticoid Receptor Gene May Be Associated with an Increased Sensitivity to Glucocorticoids in Vivo

We investigated whether a polymorphism at nucleotide position 1220, resulting in an asparagine-to-serine change at codon 363 in the glucocorticoid receptor (GR) gene is associated with an altered sensitivity to glucocorticoids.In a group of 216 elderly persons, 13 heterozygotes for the N363S polymorphism were identified by PCR/single strand conformation polymorphism analysis.In 2 dexamethasone (DEX) suppression tests (DSTs), using 1 and 0.25 mg DEX, the circulating cortisol and insulin concentrations were compared between N363S carriers and controls.In the 1-mg DST, there were no differences between N363S carriers and controls, with respect to adrenal suppression, but there was a significantly higher (P 0.05) insulin response in N363S carriers.In the 0.25-mg DST, a significantly larger (P 0.05) cortisol suppression and higher (P 0.05) insulin response were seen in N363S carriers.Comparison of blood pressure, body mass index (BMI), and bone mineral density (BMD) between the N363S carriers and controls showed that N363S carriers had a higher (P 0.05) BMI but normal blood pressure.There was an obvious trend towards lower age-, BMI-,