[Possible pathogenetic role of 11 beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) gene polymorphisms in arterial hypertension].

Abstract

BACKGROUND:

Cortisol has been implicated in hypertension and lately reported to be regulated at the pre-receptor level by the 11betaHSD1 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 11betaHSD2 impaired patients. Several polymorphisms have been reported in HSDl IB 1 gene (CAI5, CAI9 and InsA83557), which could modify HSDl IB 1 gene expression or activity.

AIM:

To determine the distribution and prevalence of CAI5, CAI9 and InsA83557 in the HSDl IBl 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 índex >30 kg/m(2)) and 30 normotensive adults (NT). In each patient, we measured serum levels of E 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 CAI5 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 InsA83557polymorphism 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 CAI5 and CAI9 polymorphism correlated with changes in biochemical parameters in HPA and RAA axis of obese essential hypertensives. These changes may result in modifications in the expression of 11betaHSD1, leading to increased cortisol and aldosterone levels independent of ACTH and renin control, respectively.

• Authors: Mauricio A Morales, Cristián A Carvajal, Eugenia Ortiz, Lorena M Mosso, Rocío A Artigas, Gareth I Owen, Carlos E Fardella
• Journal: Revista medica de Chile (Rev Med Chil) Vol. 136 Issue 6 Pg. 701-10 (Jun 2008) ISSN: 0034-9887 [Print] Chile
• Vernacular Title: Regiones polimórficas del gen 11 beta-hidroxiesteroide deshidrogenasa tipo 1 (11betaHSD1) en hipertensión arterial esencial: Posible rol etiopatogénico.
• PMID: 18769825 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aldosterone
• Adrenocorticotropic Hormone
• 11-beta-Hydroxysteroid Dehydrogenase Type 1
• HSD11B1 protein, human
• Renin
• Cortisone
• Hydrocortisone

Topics

• 11-beta-Hydroxysteroid Dehydrogenase Type 1 (genetics, metabolism)
• Adrenocorticotropic Hormone (blood)
• Adult
• Aldosterone (blood)
• Case-Control Studies
• Chronic Disease
• Cortisone (biosynthesis)
• Female
• Gene Frequency
• Humans
• Hydrocortisone (blood)
• Hypertension (enzymology, genetics)
• Male
• Microsatellite Repeats
• Obesity (enzymology, genetics)
• Polymerase Chain Reaction
• Polymorphism, Genetic
• Renin (blood)
• Young Adult