Role of glucocorticoid receptor SNPs in receptor function and metabolic disease

Wednesday, October 26, 2011 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center	NIEHS	CLIN/CULT/AGING/DISPREV-19

Authors

• L Murphy
• S Garantziotis
• J Cidlowski

Abstract

The role of glucocorticoid receptor SNPs in receptor function and metabolic disease is being studied at the National Institute of Environmental Health Sciences (NIEHS). This in vivo and in vitro observational gene association study investigates functional relevance of SNPs in the NR3C1 gene. Individuals with and without functionally relevant, novel SNPs are identified and recruited from Environmental Polymorphism Registry (EPR). EPR is a DNA biorepository of over 15,000 participants developed at NIEHS to help researchers better understand relationships between environmental exposures, genetic susceptibility and disease. Primary objective is to investigate in vivo hGR SNPs’s (hGR9beta A3669G, hGR N363S) role in steroid responsiveness using dexamethasone and comparing serum cortisol levels by genotype. Initial comparisons indicate some hGR9betaA3669G carriers are resistant to dexamethasone. Secondary objective is to investigate hGR SNPs’s (hGR9betaA3669G, hGR N363S) role in human steroid responsiveness by comparing gene expression profiles of macrophages exposed ex vivo to corticosteroids. A pilot microarray study on macrophages without hGR SNPs revealed that although there is great variability in gene regulation between individuals, treatment with dexamethasone significantly altered gene regulation. This study is the first EPR study conducted at NIEHS Clinical Research Unit and will help define and enhance operations of future EPR studies.

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