Associations of glucocorticoid receptor and corticosteroid-binding globulin gene polymorphisms on fat mass and fat mass distribution in prepubertal obese children

Previous studies conducted in adult obese patients have shown that glucocorticoid receptor and corticosteroid-binding globulin gene polymorphisms influence cortisol-driven obesity and metabolic parameters. We investigated the impact of these polymorphisms in prepubertal obese children that were thoroughly examined for hypothalamic?Cpituitary?Cadrenal axis activity and for metabolic and obesity parameters. Obese children carrier of the allele G of the BclI polymorphism within glucocorticoid receptor gene tend to present a higher percentage of fat mass as well as a decreased cortisol suppression after low-dose dexamethasone as found in adult studies. Additionally, these allele G carriers show a strong correlation between truncal fat mass distribution and cortisol response to a standardized lunch, whereas this correlation is weak in allele C carriers. No differences were found for obesity or metabolic parameters between genotypes at the corticosteroid-binding globulin locus. However, allele 90 carriers present increased 24-h free urinary cortisol. Overall, this study provides new data showing the influence of glucocorticoid receptor and corticosteroid-binding globulin genes in obesity and/or cortisol action in prepubertal obese children.