HIPERTENSI SEKUNDER: GEN-GEN YANG MERANGSANG PEREMBESAN ALDOSTERON YANG BERLEBIHAN

Abstract

Hypertension is highly prevalent in Malaysia and even the rest of the world. Primary aldosteronism (PA) is one of the most common treatable cause of secondary hypertension. PA occurs due to excessive secretion of aldosterone in the adrenal glands. Up to one in five resistant hypertension cases are due to PA. Therefore, there are a high number of individuals who have the potential to be cured of their hypertension. However, this is difficult to achieve due to limitations in the procedure of diagnosing the PA disease. The challenge now is to know the best usage of available diagnostic methods to detect those who would most likely be cured of hypertension which may be associated with the genotype of the disease. In the past decade, five genes have been found to cause excess aldosterone production in aldosteroneproducing adenomas (APAs), namely KCNJ5, ATP1A1, ATP2B3, CACNA1D and CTNNB1. These somatic mutations have been found to activate the intracellular signaling pathway that regulates aldosterone production. Studies on bilateral adrenal hyperplasia (BAH) samples also have identified the genetic causes for the many hereditary hyperaldosteronism, namely familial hyperaldosteronism types I, II, III, and IV/V. Herein we review the genetic factors of PA as a result of either aldosterone-stimulating somatic mutations or germline variants, and the associated clinical phenotype. Keywords: Primary aldosteronism; hypertension; hyperaldosteronism; mutation