title: Impact of mineralocorticoid receptor polymorphisms on urinary electrolyte excretion with and without diuretic drugs.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  rs3857080 may be a promising new candidate for research in cardiac and renal disorders and on antialdosteronergic drugs like spironolactone.
authors.affiliation: Institute of Clinical Pharmacology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Nawar
authors.initials: N
authors.lastname: Dalila
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brockmöller
authors.forename: Mladen Vassilev
authors.initials: MV
authors.lastname: Tzvetkov
authors.forename: Markus
authors.initials: M
authors.lastname: Schirmer
authors.forename: Martin
authors.initials: M
authors.lastname: Haubrock
authors.forename: Stefan Viktor
authors.initials: SV
authors.lastname: Vormfelde
mesh_terms: D000293:Adolescent; D000328:Adult; D002034:Bumetanide / Q000494:pharmacology; D018592:Cross-Over Studies; D004232:Diuretics / Q000494:pharmacology*; D004573:Electrolytes / Q000652:urine*; D005665:Furosemide / Q000494:pharmacology; D056726:Genetic Association Studies; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011188:Potassium / Q000652:urine; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000235:genetics*; D016037:Single-Blind Method; D012965:Sodium Chloride / Q000652:urine; D013449:Sulfonamides / Q000494:pharmacology; D000077786:Torsemide; D014223:Triamterene / Q000494:pharmacology; D055815:Young Adult
chemical_list: D004232:Diuretics; D004573:Electrolytes; D018161:Receptors, Mineralocorticoid; D013449:Sulfonamides; D006852:Hydrochlorothiazide; D002034:Bumetanide; D012965:Sodium Chloride; D005665:Furosemide; D011188:Potassium; D000077786:Torsemide; D014223:Triamterene
keywords: LHX4; NR3C2; aldosterone; antihypertensive agents; hydrochlorothiazide; loop diuretics; mineralocorticoid receptor; pharmacogenetics; polymorphisms; triamterene