Evaluation of Links Between High-Density Lipoprotein Genetics, Functionality, and Aortic Valve Stenosis Risk in Humans

作者：Arsenault Benoit J; Dube Marie Pierre; Brodeur Mathieu R; de Oliveira Moraes Adriana Benjamin; Lavoie Veronique; Kernaleguen Anne Elen; Guauque Olarte Sandra; Mathieu Patrick; Pibarot Philippe; Messika Zeitoun David; Bosse Yohan; Rhainds David; Rheaume Eric; Tardif Jean Claude^*

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2014, 34(2): 457-462.

DOI：10.1161/ATVBAHA.113.302730

• aortic valve stenosis
• cholesterol efflux capacities
• coronary artery disease
• high-density lipoproteins
• human genetics

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 P0.05 for all single nucleotide polymorphisms tested). In a subsample of this cohort, HDL cholesterol levels, apolipoprotein AI levels, lecithin-cholesterol acyltransferase activity, pre--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 (P0.003), 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.

• 出版日期2014-2