title: Evaluation of links between high-density lipoprotein genetics, functionality, and aortic valve stenosis risk in humans.
abstract: OBJECTIVE
  Studies have shown that high-density lipoprotein (HDL)-raising compounds induce regression of aortic valve stenosis (AVS) in animal models. However, whether patients with AVS have an impaired HDL metabolism is unknown.
  
  
  RESULTS
  A total of 1435 single nucleotide polymorphisms in genes associated with HDL cholesterol levels (in or around GALNT2, LPL, ABCA1, APOA5, SCARB1, LIPC, CETP, LCAT, LIPG, APOC4, and PLTP) were genotyped in 382 patients with echocardiography-confirmed AVS (aortic jet velocity ≥2.5 m/s) and 401 controls. After control for multiple testing, none of the genetic variants showed a positive association with case/control status (adjusted P≥0.05 for all single nucleotide polymorphisms tested). In a subsample of this cohort, HDL cholesterol levels, apolipoprotein AI levels, lecithin-cholesterol acyltransferase activity, pre-β-HDL, HDL size, and 4 parameters of cholesterol efflux capacity were measured in apolipoprotein B-depleted serum samples from 86 patients with and 86 patients without AVS. Cholesterol efflux capacity was measured using J774 macrophages with and without stimulation of ATP-binding cassette A-1 expression by cAMP, and HepG2 hepatocytes for scavenger receptor class B type 1-mediated efflux. None of these parameters were different between cases and controls. However, compared with patients without coronary artery disease, sera from patients with coronary artery disease had lower HDL cholesterol levels, scavenger receptor class B type 1-mediated efflux, and HDL size (P≤0.003), independently of the presence or absence of AVS.
  
  
  CONCLUSIONS
  Results of the present study suggest that, based on HDL genetics and HDL functionality, HDL metabolism does not seem to predict the risk of AVS. Because of our limited sample size, additional studies are needed to confirm these findings.
authors: From the Montreal Heart Institute, Montreal, Canada (B.J.A., M.-P.D., M.R.B., A.B.d.O.M., V.L., A.-E.K., D.R., É.R., J.-C.T.); Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, Canada (B.J.A., M.-P.D., M.R.B., A.B.d.O.M., É.R., J.-C.T.); Beaulieu-Saucier Université de Montréal Pharmacogenomics Centre, Montreal, Canada (M.-P.D., J.-C.T.); Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec (S.G.-O., P.M., P.P., Y.B.) and Department of Molecular Medicine (Y.B.), Laval University, Québec, Canada; Cardiology Department, AP-HP, Bichat Hospital, Paris, France (D.M.-Z.); and INSERM U698, University Paris 7, Paris, France (D.M.-Z.).
authors: Benoit J
authors: BJ
authors: Arsenault
authors: Marie-Pierre
authors: MP
authors: Dubé
authors: Mathieu R
authors: MR
authors: Brodeur
authors: Adriana Benjamin
authors: AB
authors: de Oliveira Moraes
authors: Véronique
authors: V
authors: Lavoie
authors: Anne-Elen
authors: AE
authors: Kernaleguen
authors: Sandra
authors: S
authors: Guauque-Olarte
authors: Patrick
authors: P
authors: Mathieu
authors: Philippe
authors: P
authors: Pibarot
authors: David
authors: D
authors: Messika-Zeitoun
authors: Yohan
authors: Y
authors: Bossé
authors: David
authors: D
authors: Rhainds
authors: Eric
authors: E
authors: Rhéaume
authors: Jean-Claude
authors: JC
authors: Tardif
mesh_terms: D000368:Aged; D000818:Animals; D001021:Aortic Valve / Q000000981:diagnostic imaging / Q000503:physiopathology; D001024:Aortic Valve Stenosis / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000235:genetics*; D016015:Logistic Models; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D010297:Paris; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011792:Quebec; D012307:Risk Factors; D014463:Ultrasonography
chemical_list: D008076:Cholesterol, HDL; D005819:Genetic Markers; D008075:Lipoproteins, HDL
keywords: aortic valve stenosis; cholesterol efflux capacities; coronary artery disease; high-density lipoproteins; human genetics