Possible pathogenetic role of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) gene polymorphisms in arterial hypertensionRegiones polimórficas del gen 11β-hidroxiesteroide deshidrogenasa tipo 1 (11βHSD1) en hipertensión arterial esencial: Posible rol etiopatogénico
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Date
2008
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Abstract
Background: Cortisol has been implicated in hypertension and lately reported to be regulated at the pre-receptor level by the 11βHSD1 enzyme, which converts cortisone (E) to cortisol (F). Over expression of this enzyme in adipose tissue could determine an increase in available cortisol that interacts with the mineralocorticoid receptor (MR) in renal, brain and heart tissue, leading to similar hypertensive effects as in 11βHSD2 impaired patients. Several polymorphisms have been reported in HSD11B1 gene (CA15, CA19 and InsA83557), which could modify HSD11B1 gene expression or activity. Aim: To determine the distribution and prevalence of CA15, CA19 and InsA83557 in the HSD11B1 gene, and to correlate these results with biochemical parameters in cortisol/ACTH (HPA) and renin-angiotensin-aldosterone (RAA) axis in patients with essential hypertension (EH). Patients and Methods: We studied 113 EH patients (76 non-obese and 37 obese, with a body mass index >30 kg/m 2) and 30 normotensive adults (NT). In each patient, we measured serum levels of F, E, serum aldosterone (SA), plasma renin activity (PRA), adrenocorticotrophic hormone (ACTH), the urinary free cortisol/creatinine (UFF/Cr), F/ACTH and SA/PRA ratios. Each polymorphism was studied by PCR and 8% polyacrylamide gel electrophoresis. Statistical associations were evaluated by Pearson correlations and the genetic equilibrium by the Hardy-Weinberg (H-W) equation. Results: We found all three polymorphisms in the EH and the NT group, both in genetic equilibrium. In obese essential hypertensives, the CA15 polymorphism showed association with SA/PRA ratio (r =0.189, p =0.012) and F/ACTH (r =0.301, p 0.048); CA19 also showed correlation with F/ACTH in obese EH (r =-0.220, p 0.009). The InsA83557 polymorphism correlated with UFF/Cr in both EH (r =0.206; p =0.03), and in obese EH (r =0.354; p =0.05). Conclusions: The CA15 and CA19 polymorphism correlated with changes in biochemical parameters in HPA and RAA axis of obese essential hypertensives. These changes may result of modifications in the expression of 11βHSD1, leading to increased cortisol and aldosterone levels independent of ACTH and renin control, respectively.
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Keywords
11-beta-hydroxysteroid dehydrogenase type 1, Hypertension, Polymorphism, genetic