Genetic variability in CRHR1 and its association with participant response to glucocorticoid receptor-mediated signaling (776.2)

The goal of this study was to identify correlations between interpersonal genetic variability and alterations in the intracellular glucocorticoid receptor (GR)-mediated signaling pathway. Salivary cortisol concentrations were measured in healthy volunteers (n=66) in order to determine differences in circulating cortisol concentrations and cortisol response to HPA stimulation. Statistical analysis indicated inter-participant cortisol variability was not correlated to participant demographics, health history, or SNPs in genes encoding the GR (NR3C1) or the essential GR chaperone protein hsp90 (HSP90AA1). Two participants with highly similar demographic profiles and opposing responses to HPA stimulation were selected for matched exome sequencing. Filtering analysis identified candidate SNPs in approximately 30 genes involved in mediating the cortisol response and GR signaling. Interestingly, corticotropin releasing hormone receptor 1 (CRHR1) showed a difference of over 20 SNPs between the matched exome pair....