Pharmacogenomics of the Variability in the In Vivo Response to Glucocorticoids

Pharmacogenomics of the Variability in the In Vivo Response to Glucocorticoids

This study evaluates the effect of acute administration of oral prednisone in white blood cells counts and glucose tolerance and the relationship of these measures with changes in gene expression in healthy volunteers. White blood cells counts, glucose tolerance and gene expression will be study before and after prednisone administration.

Prednisone is a potent anti-inflammatory drug that has large variability in its response. The large inter individual variability in the response to prednisone has a genetic component, but the genetic determinants of this variability remain unknown. We propose to use two relevant phenotypes, changes in white blood cell counts and changes in glucose tolerance induced by in vivo administration of prednisone, to characterize gene expression patterns and identify variants that are involved in the in vivo response to prednisone.

Inclusion Criteria:

• 18 to 45 years old (to exclude the effect of age on glucose tolerance);
• BMI between 20 and 25 kg/m2 (to exclude individuals that are likely to have impaired insulin response);
• Normal fasting glucose;
• Stable weight for three months before participation

Exclusion Criteria:

• BMI >25kg/m2;
• Fasting glucose ≥126 mg/dl
• Shift work or disordered sleep (to exclude individuals with alterations in the hypothalamus-adrenergic axis);
• Any diseases;
• Use of any medication regularly (including over-the-counter);
• Previous exposure to glucocorticoids (within the last year);
• Pregnancy