title: The genetics of loop diuretic effects.
abstract: Little is known about the genetic impact on loop diuretic effects. We newly investigated five genetic polymorphisms in 95 healthy volunteers, who had ingested bumetanide, frusemide and torsemide. The subjects excreted means of 20.2 g sodium chloride, 2.87 g potassium and 261 mg calcium over 24 h. Concerning sodium chloride, the subjects excreted 2.2 g less per two T-alleles of C825T in the G nucleotide β-subunit 3 (GNB3), 3.2 g less per two Met32-alleles of Val32Met in the atrial natriuretic peptide precursor (ANP) and 2.8 g more per two Arg152-alleles of Ter152Arg in ANP (P=0.007, 0.05 and 0.007). Concerning potassium, the subjects excreted 0.42 g more per two ANP Arg152-alleles (P=0.023). Concerning calcium, the subjects excreted 32 mg more per two deletion-alleles of the insertion/deletion polymorphism in the angiotensin-converting enzyme, 44 mg more per two Trp460-alleles of Gly460Trp in α-adducin (ADD1) and 42 mg less per two GNB3 T-alleles (P=0.006, 0.023 and 0.008). The common genetic impact together with three polymorphisms in the sodium chloride cotransporter and the epithelial sodium channel was 20, 15, 10 and 23% of the variation in the urinary excretion of sodium chloride, volume, potassium and calcium. This exceeded the fraction of variation explained by differences in the pharmacokinetics: 13, 10, 11 and 6%. Thus, genetic variation seems to be a stronger predictor of the loop diuretic drug response than pharmacokinetic variation.
authors.affiliation: Department of Clinical Pharmacology, University Medical Center, Georg-August-University, Göttingen, Germany. svormfe@gwdg.de
authors.forename: S V
authors.initials: SV
authors.lastname: Vormfelde
authors.forename: J
authors.initials: J
authors.lastname: Brockmöller
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004232:Diuretics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology*; D014882:Water-Electrolyte Balance / Q000235:genetics
chemical_list: D004232:Diuretics; D049994:Sodium Potassium Chloride Symporter Inhibitors