The Role of Glucocorticoid Receptor SNPs in Receptor Function and Metabolic Disease
- Glucocorticoids are primary stress response hormones released from the adrenal gland when an individual is under stress. Chronic or ongoing elevation of these hormones due to prolonged stress or medical treatments can have numerous harmful effects. Researchers are interested in learning more about how these hormones affect cell growth, development, and death. To study glucocorticoid hormones, researchers plan to use the medication dexamethasone, which affects the parts of cells that respond to glucocorticoid hormones.
- To study glucocorticoid stress hormones in healthy individuals before and after receiving dexamethasone.
- Healthy individuals at least 18 years of age.
- Participants must not be using certain medications that may affect the dexamethasone test, including hormonal contraception, steroid-based drugs, and some antidepressants.
- This study will require an initial screening visit and a second study visit. The visits are estimated to require about 1 to 2 hours of participation over a period of up to 14 days.
- Participants will be screened at visit 1 with a full physical examination and medical history, and an initial blood sample for testing.
- For visit 2, participants will be asked to abstain from all food and drinks except for water for 12 hours before the appointment, and will take one tablet of dexamethasone 9 hours before the appointment.
- Participants will have a second blood sample taken during visit 2, and will receive a snack after the blood is drawn.
Connective Tissue Metabolism
|Official Title:||The Role of Glucocorticoid Receptor SNPs in Receptor Function and Metabolic Disease|
|Study Start Date:||May 2010|
This in vivo and in vitro observational gene association study will investigate the functional relevance of SNPs in the NR3C1 gene in selected populations. A subgroup of the EPR will be genotyped to identify novel SNPs in the NR3C1 gene. The most promising SNPs for functional relevance in in vitro assays will be examined. Individuals with and without functionally relevant, novel SNPs will be recruited for further study. In part 1, lymphocytes from these participants will be isolated, exposed ex vivo to corticosteroids, and gene expression profiles in response to this stimulus will be compared. In part 2, in vivo effect of these SNPs in steroid responsiveness will be evaluated by performing a modified low dose dexamethasone suppression test comparing by genotype. The study design is innovative as a gene association study in the sense that participants are recruited on the basis of genotype and then the phenotype of each participant is observed.
It is anticipated that the study will require 48 months to complete participants study visits.
Investigate in vivo the role of hGR SNPs (hGR9beta A3669B, hGR N363S) in steroid responsiveness by performing a modified dexamethasone suppression test and comparing responses by genotype.
Investigate the role of hGR SNPs (hGR9beta A3669B, hGR N363S) in human steroid responsiveness by comparing (across genotypes) gene expression profiles of isolated macrophages and lymphocytes exposed ex vivo to corticosteroids.
Measure the change in serum cortisol levels after modified dexamethasone suppression test.
Measure gene expression fold changes by microarray analysis after ex vivo glucocorticoid exposure of macrophages and lymphocytes; validation of affected RNA (elevated or decreased expression) through PCR analysis.
|Contact: Lisa B Murphy||(919) firstname.lastname@example.org|
|Contact: Stavros Garantziotis, M.D.||Not Listedemail@example.com|
|United States, North Carolina|
|NIEHS Clinical Research Unit (CRU)||Recruiting|
|Research Triangle Park, North Carolina, United States|
|Contact: Lisa Murphy 919-541-9839 firstname.lastname@example.org|
|Principal Investigator:||Stavros Garantziotis, M.D.||National Institute of Environmental Health Sciences (NIEHS)|