The Linkage Between 11β-hydroxysteroid Dehydrogenase Type 1 Enzyme Hyperactivity Polymorphisms & Metabolic Syndrome

A diagnosis of Metabolic Syndrome (MSX) requires patients to present with three or more of the following symptoms: elevated fasting blood glucose levels, elevated serum triglyceride levels, low serum HDL levels, elevated blood pressure, and truncal obesity.  This pathology shares many similarities with Cushing’s Syndrome (CS) but a diagnosis of CS requires hypercortisolemia.  This similarity has led our lab and others to hypothesize that MSX may be a Cushingoid-like state caused by hyperactivity of the cortisol reductase enzyme, also know as 11β-hydroxysteroid dehydrogenase, type 1 (11β-HSD1) .  The 11β-HSD1 enzyme is responsible for the conversion of inactive cortisone to cortisol, and works primarily in the adipose tissue.  Using an allele specific PCR assay for previously identified single nucleotide polymorphisms (SNP) within the 11β-HSD1 enzyme (rs12086634 and rs846910), we have observed  these polymorphisms present at a higher frequency in a population of patients seeking bariatric (weight-loss) surgery when compared to a control population or reported frequencies.  In our patient population, the frequency of heterozygosity for the rs12086634 SNP was nearly 50% higher than the reported frequency in the general population, suggesting that this polymorphism may contribute to increased obesity and the MSX metabolic profile by increasing the localized cortisol in adipose tissue.  Greater understanding of the interplay between these and related single nucleotide polymorphisms can help physicians and patients make more informed decisions about treatment options for obesity and metabolic syndrome.