Mineralocorticoid receptor genetics: A scoping review

Abstract

The concept of the mineralocorticoid receptor (MR) has evolved to be recognized as a key regulator of blood pressure homeostasis and multisystem physiology. Beyond its classical roles in renal sodium and water balance, MR activity influences cardiovascular, metabolic, and neurological processes, among others. Advancing our understanding of MR is essential for: (1) Improving pharmacological MR modulation; (2) Optimizing experimental and translational models; and (3) Enhancing the clinical data interpretation. Although substantial progress has been made in elucidating MR molecular biology, knowledge regarding its genetic remains limited. Considering the potential impact of genetic variants on MR structure and function, this review focuses on the current evidence surrounding MR genetics. To date, 460 germline variants of the MR gene have been reported, primarily associated with two phenotypes: (1) Autosomal dominant early-onset hypertension exacerbated during pregnancy; and (2) Autosomal dominant pseudohypoaldosteronism type-I. Therefore, genetics provides a framework for connecting molecular alterations of MR with clinical phenotypes, deepening our understanding of interindividual variability and enabling the development of personalized therapeutic strategies.