Obesity is a product of multiple comorbidities ,such as elevated blood pressure, serum triglycerides, and blood sugar. All of these factors are affected by nuclear hormone receptors that regulate gene expression. The glucocorticoid receptor (GR), is one example of these nuclear hormone receptors. The GR binds glucocorticoids, most importantly, cortisol, which controls factors that contribute to obesity. Specific polymorphisms of the GR, the mineralocorticoid receptor (MR), heat shock protein 90 (HSP90) and 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD1) have been found in our labs and others to be present at high frequency in obese populations. One new gene of interest is the FK506 binding protein (FKBP), a co-chaperone that works in conjunction with HSP90 to negatively regulate GR activity. It is hypothesized that polymorphisms exist in the FKBP51 gene that would result in decreased activity of FKBP and subsequent overactivity of GR resulting in phenotypic hypercortisolemia. Analysis of the FKBP51 single nucleotide polymorphism RS1360780 showed a correlation with serum triglycerides, blood pressure, BMI, in bariatric surgery patients. This finding, in combination with previous results, will lead to a better understanding of the genetic underpinnings of obesity.
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