Investigating the Role of Cortisol Sensitivity SNP rs2918419 in Metabolic Syndrome

Cortisol, a glucocorticoid, is the human body’s natural stress hormone. When cortisol is released its signal elevates blood sugar (glucose) levels and triggers other responses to prepare the body’s fight-or-flight response. Cortisol provides many benefits to the human body and is essential to survival but in excess, it can lead to health complications. Excess amounts of cortisol (hypercortisolism) leads to Cushing’s syndrome. Symptoms of Cushing’s syndrome include high blood pressure, high blood sugar (type 2 diabetes), altered lipid profiles (including high triglycerides and low HDL), and obesity. The obesity seen in Cushing’s syndrome is a very specific type of obesity called centripetal obesity with a high level of visceral fat (around internal organs in the abdominal cavity) and a very large waist circumference. Metabolic syndrome is a specific subtype of obesity that shares many characteristics with Cushing’s syndrome; a person has metabolic syndrome if three or more of the previous five criteria are met. The difference between patients with Cushing’s syndrome and metabolic syndrome are their cortisol levels (elevated versus normal, respectively). This means that some people present symptoms normally associated with elevated levels of cortisol without having elevated cortisol levels – suggesting that their bodies are more sensitive to cortisol. We hypothesized that hypersensitivity of the glucocorticoid receptor to normal or even reduced levels of cortisol contributes to the pathogenesis of metabolic syndrome. Based on this hypothesis, our study is investigating the single nucleotide polymorphism (SNP) rs2918419 which has been linked with hyperinsulinemia (the amount of insulin in the blood is higher than what's considered healthy) – a cause of weight gain and frequently associated with elevated blood sugar, both of which are symptoms of metabolic syndrome. Using qPCR allele frequency, the SNP is being compared to symptoms of metabolic syndrome in a population of people with obesity. We anticipate that the mutant allele of rs2918419 will be seen in a higher frequency in patients exhibiting symptoms of metabolic syndrome. Since obesity rates in the US have jumped from 13% to 40% in the last 50 years, and are only increasing, identifying genetic markers for metabolic syndrome could help identify ways to predict or treat this medical disorder.