SOMATIC MUTATIONS OF THE ANGIOTENSIN-II (AT(1)) RECEPTOR GENE ARE NOTPRESENT IN ALDOSTERONE-PRODUCING ADENOMA

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 (AT(1)). 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, possibl e that primary hyperaldosteronism caused by an aldosterone producing a denoma (APA) may be the result of constitutive activation of the AT(2) receptor. The 1.1-kilobase coding region (exon 5) of the AT(1) recept or gene was analysed in APA and normal adrenal tissue for the presence of mutations using single stranded conformational polymerphism and se quencing techniques. In 17 APAs, no functional mutations were found th at could account for the observed pathophysiology. However, three sile nt polymorphisms were detected in regions encoding the second extracel lular loop, the intracellular arm preceding the COOH terminal, and the 3'-untranslated region. In conclusion, somatic mutations in the codin g region of the AT(1) receptor gene do not appear to play a role in pr imary hyperaldosteronism caused by an APA.