Date of Award

6-2016

Document Type

Open Access

Degree Name

Bachelor of Science

Department

Neuroscience

First Advisor

Brian D. Cohen

Abstract

Cortisol acts on target tissues through the glucocorticoid receptor (GR). When in high concentration in the blood, it causes an obesity phenotype with hyperglycemia, hyperglyceridemia, hypertension and weight gain, known as Cushings’ Syndrome or Disease (CS/D). Hypersensitivity-causing single-nucleotide polymorphisms (SNPs) of the GR have been shown to lead to a similar phenotype. Because of the symptomatic resemblance between CS/D and Metabolic Syndrome (MS), we and others hypothesized that the MS may be a Cushingoid-like state with absence of hypercortisolemia, but with GR hypersensitivity. Additionally, the link between GR SNPs and the success of bariatric surgery as measured by the percent of excess body weight loss (%EBWL) following bariatric surgery has been largely left untested.

We tested 62 obese bariatric patients and 51 normal weight college students for the presence of the BclI and N363S SNPs using a polymerase chain reaction technique with allele-specific primers. We first compared the prevalence of the SNPs in our populations and found them to be higher in the obese population for both SNPs. We also obtained a variety of metabolic parameters on the bariatric population and looked for significant differences across genotypes using one-way ANOVAs. Homozygous mutants for the BclI SNP showed a significant difference in triglyceride levels from heterozygotes. While all other parameters were non-significant, BclI mutants tended to have higher LDL cholesterol levels and lower HDL cholesterol levels with only slightly higher BMI, and N363S heterozygotes seemed to have higher LDL levels, systolic BP and blood glucose than homozygous wild-types. Our only BclI-positive/N363S-positive patient also tended to have higher blood glucose, LDL cholesterol, and systolic blood pressure, when compared to BclI-positive/N363S-negative patients. Finally, BclI-positive patients who underwent a gastric band tended to lose less weight following bariatric surgery than patients on whom other weight-loss surgeries were performed.

Taken together, these results support the hypothesis that GR SNPs have a significant impact on metabolic profiles, suggesting that GR SNPs could contribute to the development of disease states such as the MS, and affect the success of gastric band surgery.

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