Impact of mineralocorticoid receptor polymorphisms on urinary electrolyte excretion with and without diuretic drugs

Aim: Polymorphisms in the mineralocorticoid receptor may affect urinary sodium and potassium excretion. We investigated polymorphisms in the MR gene in relation to urinary electrolyte excretion in two separate studies. Patients & methods: The genotype-phenotype association was studied in healthy volunteers after single doses of bumetanide, furosemide, torsemide, hydrochlorothiazide, triamterene and after NaCl restriction. Results: High potassium excretion under all conditions except torsemide, and high NaCl excretion after bumetanide and furosemide were associated with the A allele of the intron-3 polymorphism (rs3857080). This polymorphism explained 5-10% of the functional variation and in vitro, rs3857080 affected DNA binding of the transcription factor LHX4. Conclusion: rs3857080 may be a promising new candidate for research in cardiac and renal disorders and on antialdosteronergic drugs like spironolactone. Original submitted 23 June 2014; Revision submitted 5 November 2014