Lack of mutations of type 1 11 beta-hydroxysteroid dehydrogenase gene in patients with abdominal obesity

There is increasing evidence that in human obesity, particularly the abdominal phenotype, the activity of the hypothalamic-pituitary-adrenal (HPA) axis is disregulated. At least two distinct alterations have been reported: one is characterized by several neuroendocrine abnormalities and hyperresponsiveness of the HPA axis to different neuropeptides, the other is characterized by elevated cortisol traffic and probably by supranormal cortisol production. The 11 beta -hydroxysteroid dehydrogenase (11 beta -HSD) enzymes interconvert cortisol and cortisone in human. Two different isoforms have been identified. A possible modification of the activity of the enzyme 11 beta -HSD1 in subjects with abdominal obesity has been described in the literature. We decided to test the hypothesis that mutated isoforms of type 11 beta -HSD1 protein could be responsible for alterations of cortisol metabolism in patients with abdominal obesity. A mutational screening of the whole coding sequence and exon-flanking regions of the 11 beta -HSD1 gene has been performed in 8 patients. The main results of our study are the exclusion of a common association of 11 beta -HSD1 mutations to obesity and the identification of two novel allelic variants for the gene 11 beta -HSD1 in the Italian population, not previously described in any database.