Assessing Glucocorticoid Receptor Polymorphisms in Obese Populations

The glucocorticoid receptor (GR) is part of a family of nuclear receptors that control gene expression. In the presence of the steroid hormone cortisol, certain genes are expressed; the products of which control certain features of the body, including but not limited to, blood pressure, serum triglycerides, and blood sugar. There is evidence that these features are major contributors to obesity. Specific polymorphisms of the GR and other regulators of either GR or the closely related mineralocorticoid receptor such as heat shock protein 90 (HSP90) and 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD1)  have been found in our labs and others to be present at a higher frequency in obese populations. Our current research is investigating polymorphisms in these genes as well as the gene encoding the FK506 binding protein (FKBP) which works in conjunction with HSP90 to negatively regulate GR activity. This finding in combination with previous results will lead to a better understanding of the genetic underpinnings of obesity and may reveal novel therapeutic approaches. These polymorphisms will be assessed in relation to post-operative features of bariatric surgery, analyzing whether or not there is a correlation with weight regain after bariatric surgery in the presence of certain mutations.