Evaluation of links between high-density lipoprotein genetics, functionality, and aortic valve stenosis risk in humans

Arterioscler Thromb Vasc Biol. 2014 Feb;34(2):457-62. doi: 10.1161/ATVBAHA.113.302730. Epub 2013 Dec 12.


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.

Approach and 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.

Keywords: aortic valve stenosis; cholesterol efflux capacities; coronary artery disease; high-density lipoproteins; human genetics.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Aortic Valve / diagnostic imaging
  • Aortic Valve / physiopathology
  • Aortic Valve Stenosis / blood
  • Aortic Valve Stenosis / diagnostic imaging
  • Aortic Valve Stenosis / genetics*
  • Aortic Valve Stenosis / physiopathology
  • Case-Control Studies
  • Chi-Square Distribution
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / genetics
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / genetics
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Hep G2 Cells
  • Hepatocytes / metabolism
  • Humans
  • Lipoproteins, HDL / blood
  • Lipoproteins, HDL / genetics*
  • Logistic Models
  • Macrophages / metabolism
  • Male
  • Mice
  • Middle Aged
  • Paris
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Quebec
  • Risk Factors
  • Ultrasonography


  • Cholesterol, HDL
  • Genetic Markers
  • Lipoproteins, HDL