title: [Subclinical endothelial inflammation markers in a family with type I familial hyperaldosteronism caused by a de novo mutation].
abstract: BACKGROUND
  Type I familial hyperaldosteronism is caused by the presence of a chimaeric gene CYPl 1B1/CYP11BZ which encodes an enzyme with aldosterone synthetase activity regulated by adrenocorticotrophic hormone (ACTH). Therefore, in patients with FH I is possible to normalize the aldosterone levels with glucocorticoid treatment. Recently it has been shown that aldosterone plays a role in the production of endothelial oxidative stress and subclinical inflammation.
  
  
  OBJECTIVE
  To evaluate subclinical endothelial inflammation markers, like Metalloproteinase 9 (MMP-9) and ultrasensitive C reactive protein (usPCR), before and after glucocorticoid treatment in family members with FH-I caused by a de novo mutation.
  
  
  METHODS
  We report three subjects with FH-I in a single family (proband, father and sister). We confirmed the presence of a chimaeric CYPl 1B1/CYP11B2 gene by long-PCR in all of them. Paternal grandparents were unaffected by the mutation. The proband was a 13-year-old boy with hypertension stage 2 (in agree to The Joint National Committee VII, JNC-VII), with an aldosterone/plasma rennin activity ratio equal to 161. A DNA paternity test confirmed the parental relationship between the grandparents and father with the index case. MMP-9 and usPCR levels were determined by gelatin zymography and nephelometry, respectively.
  
  
  RESULTS
  All affected subjects had approximately a 50% increase in MMP-9 levels. Only the father had an elevated usPCR. The endothelial inflammation markers returned to normal range after glucocorticoid treatment.
  
  
  CONCLUSIONS
  We report a family carrying a FH-I caused by a de novo mutation. The elevation of endothelial inflammation markers in these patients and its normalization after glucocorticoid treatment provides new insight about the possible deleterious effect of aldosterone on the endothelium.
authors.affiliation: Departamento de Endocrinología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Carlos B
authors.initials: CB
authors.lastname: Stehr
authors.forename: Cristian A
authors.initials: CA
authors.lastname: Carvajal
authors.forename: Patricia
authors.initials: P
authors.lastname: Lacourt
authors.forename: Hernán
authors.initials: H
authors.lastname: Alcaíno
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Mellado
authors.forename: Andreína
authors.initials: A
authors.lastname: Cattani
authors.forename: Lorena M
authors.initials: LM
authors.lastname: Mosso
authors.forename: Sergio
authors.initials: S
authors.lastname: Lavandera
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Fardella
mesh_terms: D000293:Adolescent; D000450:Aldosterone / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D004730:Endothelium, Vascular; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000097:blood / Q000235:genetics*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D009154:Mutation / Q000235:genetics*; D018384:Oxidative Stress / Q000502:physiology; D010334:Paternity; D016133:Polymerase Chain Reaction / Q000379:methods; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics; D014657:Vasculitis / Q000097:blood* / Q000235:genetics
chemical_list: D015415:Biomarkers; D000450:Aldosterone; D002097:C-Reactive Protein; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D020780:Matrix Metalloproteinase 9