Somatic mutations of the ATP1A1 gene and aldosterone-producing adenomas

• Primary aldosteronism is the most common form of secondary hypertension.
• Mutations in adenomas of the KCNJ5, ATP1A1, ATP2B3 and CACNA1D have been described.
• ATP1A1 mutations result in proton or sodium leakage intracellularly.

Primary aldosteronism is the most common form of secondary hypertension. It affects approximately 10% of patients with hypertension and causes greater cardiovascular morbidity and mortality compared to essential hypertension of similar severity and duration. The cause of primary aldosteronism in about half of these patients is an aldosterone-producing adenoma; over half of these adenomas have mutations in one of several ion channels and pumps, including the potassium channel KCNJ5, calcium channel Cav1.3, α1 subunit of the sodium potassium ATPase, and membrane calcium ATPase 3. This review concentrates on the molecular and physiological mechanisms by which mutations of the ATP1A1 gene increase aldosterone production.