title: Somatic mutations of the angiotensin II (AT1) receptor gene are not present in aldosterone-producing adenoma.
abstract: Angiotensin II stimulates aldosterone secretion from the adrenal zona glomerulosa and mediates most of its biological effects via G protein-coupled type 1 angiotensin II receptors (AT1). A number of G protein-coupled receptors are constitutively activated as a result of somatic mutations in the gene encoding the protein. It is, therefore, possible that primary hyperaldosteronism caused by an aldosterone-producing adenoma (APA) may be the result of constitutive activation of the AT1 receptor. The 1.1-kilobase coding region (exon 5) of the AT1 receptor gene was analyzed in APA and normal adrenal tissue for the presence of mutations using single stranded conformational polymorphism and sequencing techniques. In 17 APAs, no functional mutations were found that could account for the observed pathophysiology. However, three silent polymorphisms were detected in regions encoding the second extracellular loop, the intracellular arm preceding the COOH terminal, and the 3'-untranslated region. In conclusion, somatic mutations in the coding region of the AT1 receptor gene do not appear to play a role in primary hyperaldosteronism caused by an APA.
authors.affiliation: INSERM U-36, Collège de France, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Davies
authors.forename: A
authors.initials: A
authors.lastname: Bonnardeaux
authors.forename: P F
authors.initials: PF
authors.lastname: Plouin
authors.forename: P
authors.initials: P
authors.lastname: Corvol
authors.forename: E
authors.initials: E
authors.lastname: Clauser
mesh_terms: D000236:Adenoma / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D000311:Adrenal Glands / Q000378:metabolism; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000096:biosynthesis*; D001483:Base Sequence; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011945:Receptors, Angiotensin / Q000235:genetics*; D012016:Reference Values
chemical_list: D011945:Receptors, Angiotensin; D000450:Aldosterone