Background: Several polymorphisms of glucocorticoid receptor (GR) gene, including BclI, N363S and ER22/23EK, which may have an influence on glucocorticoid sensitivity, have been reported. BclI and N363S polymorphisms have been associated with clinical characteristics of increased and ER22/23EK of decreased glucocorticoid (GC) effects. On the other hand, metabolic syndrome has been described in patients with adrenal incidentalomas.
Objective and participants: We investigated the relation between BclI, N363S and ER22/23EK polymorphisms in GR gene in 31 patients with adrenal incidentalomas who underwent unilateral adrenalectomy (26 women; 3676 yr old) and 117 healthy subjects (38 women; 2076 yr old). The study was approved by the Institutional Ethical Committee.
Material and method: Several metabolic and anthropometric parameters were determined in order to correlate them to the genotype. Constitutive DNA was isolated from blood leucocytes. Genotyping was performed using PCR-RFLP, allele-specific PCR method and direct DNA sequencing.
Results: The larger allele frequency of the BclI variant was significantly lower in control subjects than in patients (4.3 vs 41.9%). Similarly, N363S (2.6 vs 16.1%) and ER22/23EK (0.9 vs 3.3%) variants of GR gene were less frequent in controls. Of several variables that were significant in univariate logistic regression analyses including age, gender, BMI, hyperlipidemia, hypertension, and diabetes mellitus, independent predictors of adrenal incidentaloma were BclI genotype [P<0.001, odds ratio (OR) 22.7; 95% confidence interval (CI) 6.777.0] and homeostatic model index (RHOMA) (P=0.028, OR 1.5; CI 1.12.1).
Conclusion: BclI variant of GR gene is associated not only with metabolic syndrome but also with higher frequency of adrenal incidentalomas in population.