Aldosterone synthase activity and CYP11B2 mRNA expression were greater in mononuclear leukocytes of patients with idiopathic hyperaldosteronism than in those with adenoma or normal controls.
Case-Control
Increased aldosterone synthase activity and CYP11B2 mRNA expression in IHA patients suggest regulatory factor abnormalities rather than coding region mutations.
Idiopathic hyperaldosteronism (IHA) is characterized by hypertension with excessive production of aldosterone, potassium loss, and suppression of the renin-angiotensin system. We compared activity of aldosterone synthase and expression of CYP11B2 messenger RNA (mRNA) in mononuclear leukocytes (MNL) from patients with IHA to findings in leukocytes from patients with aldosterone-producing adenoma and normal controls. Aldosterone synthase activity was estimated from conversion of 14Cdeoxycorticosterone to 14Caldosterone. Levels of CYP11B2 mRNA were determined by competitive PCR. In the same subjects, we sought the chimeric CYP11B1/CYP11B2 that is candidate gene for glucocorticoid-remediable hyperaldosteronism. Southern blot analysis and a long PCR method were used to detect the chimeric gene. Direct sequencing of the CYP11B2 also was performed. No chimeric genes or mutations in the coding region of the CYP11B2 were found in genomic DNA from these patients. However, both aldosterone synthase activity and CYP11B2 mRNA expression were greater in mononuclear leukocytes of patients with IHA than those of patients with aldosterone-producing adenoma or controls. These results suggest that regulatory factors of the CYP11B2 gene, e.g. unidentified aldosterone-stimulating substances or abnormalities in the promoter region of the CYP11B2 gene in patients with IHA resulting in oversecretion, may cause overexpression of mRNA of CYP11B2.
Takeda et al. (Sat,) conducted a case-control in Idiopathic hyperaldosteronism. Genetic analysis of aldosterone synthase and CYP11B2 mRNA expression vs. Aldosterone-producing adenoma and normal controls was evaluated on Aldosterone synthase activity and CYP11B2 mRNA expression. Aldosterone synthase activity and CYP11B2 mRNA expression were greater in mononuclear leukocytes of patients with idiopathic hyperaldosteronism than in those with adenoma or normal controls.