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

Jürgen Brockmöller, Markus Schirmer, Stefan Viktor Vormfelde, Nawar Dalila, Mladen Vassilev Tzvetkov, Martin Haubrock

Journal: Pharmacogenomics 2016;16(2):115-27

PMID: 25616098

Abstract

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.

Address: Institute of Clinical Pharmacology, University Medical Center Göttingen, Göttingen, Germany.

DOI: 10.2217/pgs.14.163

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MeSH Terms: Adolescent, Adult, Bumetanide, Cross-Over Studies, Diuretics, Electrolytes, Furosemide, Genetic Association Studies, Humans, Hydrochlorothiazide, Male, Middle Aged, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Potassium, Receptors, Mineralocorticoid, Single-Blind Method, Sodium Chloride, Sulfonamides, Torsemide, Triamterene, Young Adult