title: A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials.
abstract: We conducted a meta-analysis of pharmacogenomic substudies of three randomized trials conducted in patients with decompensated heart failure (HF) that were led by National Heart Lung and Blood Institute (NHLBI)-funded HF Network to test the hypothesis that candidate genes modulate net fluid loss and weight change in patients with decompensated HF treated with a furosemide-based diuretic regimen. Although none of the genetic variants previously shown to modulate the effects of loop diuretics in healthy individuals were associated with net fluid loss after 72 h of treatment, a set of rare variants in the APOL1 gene, which codes for apolipoprotein L1 (P=0.0005 in the random effects model), was associated with this end point. Moreover, a common variant in the multidrug resistance protein-4 coding gene (ABCC4, rs17268282) was associated with weight loss with furosemide use (P=0.0001). Our results suggest that both common and rare genetic variants modulate the response to a furosemide-based diuretic regimen in patients with decompensated HF.
authors.affiliation: Research Center, Montreal Heart Institute, Montreal, Quebec, Canada.|Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada.|Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: de Denus
authors.affiliation: Research Center, Montreal Heart Institute, Montreal, Quebec, Canada.|Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: J L
authors.initials: JL
authors.lastname: Rouleau
authors.affiliation: Washington University School of Medicine, St Louis, MO, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Mann
authors.affiliation: Tufts Medical Center, Boston, MA, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Huggins
authors.affiliation: University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Cappola
authors.affiliation: Division of Cardiology, Duke University School of Medicine, Durham, NC, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Shah
authors.affiliation: National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Keleti
authors.affiliation: Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada.
authors.forename: Y F
authors.initials: YF
authors.lastname: Zada
authors.affiliation: Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Provost
authors.affiliation: Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Bardhadi
authors.affiliation: Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada.
authors.forename: M S
authors.initials: MS
authors.lastname: Phillips
authors.affiliation: Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Normand
authors.affiliation: Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Mongrain
authors.affiliation: Research Center, Montreal Heart Institute, Montreal, Quebec, Canada.|Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada.|Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: M-P
authors.initials: MP
authors.lastname: Dubé
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000369:Aged, 80 and over; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D002986:Clinical Trials as Topic; D005260:Female; D018495:Fluid Shifts / Q000187:drug effects; D005665:Furosemide / Q000008:administration & dosage*; D005838:Genotype; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D005665:Furosemide; D008075:Lipoproteins, HDL; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D049994:Sodium Potassium Chloride Symporter Inhibitors; C073492:ABCC4 protein, human; C108666:APOL1 protein, human