title: Acetylsalicylic acid, aging and coronary artery disease are associated with ABCA1 DNA methylation in men.
abstract: BACKGROUND
  Previous studies have suggested that DNA methylation contributes to coronary artery disease (CAD) risk variability. DNA hypermethylation at the ATP-binding cassette transporter A1 (ABCA1) gene, an important modulator of high-density lipoprotein cholesterol and reverse cholesterol transport, has been previously associated with plasma lipid levels, aging and CAD, but the association with CAD has yet to be replicated.
  
  
  RESULTS
  ABCA1 DNA methylation levels were measured in leucocytes of 88 men using bis-pyrosequencing. We first showed that DNA methylation at the ABCA1 gene promoter locus is associated with aging and CAD occurrence in men (P < 0.05). The latter association is stronger among older men with CAD (≥61 years old; n = 19), who showed at least 4.7% higher ABCA1 DNA methylation levels as compared to younger men with CAD (<61 years old; n = 19) or men without CAD (n = 50; P < 0.001). Higher ABCA1 DNA methylation levels in older men were also associated with higher total cholesterol (r = 0.34, P = 0.03), low-density lipoprotein cholesterol (r = 0.32, P = 0.04) and triglyceride levels (r = 0.26, P = 0.09). Furthermore, we showed that acetylsalicylic acid therapy is associated with 3.6% lower ABCA1 DNA methylation levels (P = 0.006), independent of aging and CAD status of patients.
  
  
  CONCLUSIONS
  This study provides new evidence that the ABCA1 epigenetic profile is associated with CAD and aging, and highlights that epigenetic modifications might be a significant molecular mechanism involved in the pathophysiological processes associated with CAD. Acetylsalicylic acid treatment for CAD prevention might involve epigenetic mechanisms.
authors.affiliation: Department of Biochemistry, Faculté de médecine et des sciences de la santé, de l'Université de Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, Québec J1H 5 N4, Canada ; ECOGENE-21 and Lipid Clinic, Chicoutimi Hospital, 305 rue St-Vallier, Saguenay, Québec G7H5H6, Canada.
authors.forename: Simon-Pierre
authors.initials: SP
authors.lastname: Guay
authors.affiliation: Department of Biochemistry, Faculté de médecine et des sciences de la santé, de l'Université de Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, Québec J1H 5 N4, Canada ; ECOGENE-21 and Lipid Clinic, Chicoutimi Hospital, 305 rue St-Vallier, Saguenay, Québec G7H5H6, Canada.
authors.forename: Cécilia
authors.initials: C
authors.lastname: Légaré
authors.affiliation: Department of Biochemistry, Faculté de médecine et des sciences de la santé, de l'Université de Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, Québec J1H 5 N4, Canada ; ECOGENE-21 and Lipid Clinic, Chicoutimi Hospital, 305 rue St-Vallier, Saguenay, Québec G7H5H6, Canada.
authors.forename: Andrée-Anne
authors.initials: AA
authors.lastname: Houde
authors.affiliation: Centre de Recherche Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, 2725 chemin Ste-Foy, Québec, Québec G1V 4G5, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mathieu
authors.affiliation: Centre de Recherche Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, 2725 chemin Ste-Foy, Québec, Québec G1V 4G5, Canada ; Department of Molecular Medicine, Université Laval, 2325 rue de l'Université, Québec, Québec G1V 0A6, Canada.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Bossé
authors.affiliation: Department of Biochemistry, Faculté de médecine et des sciences de la santé, de l'Université de Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, Québec J1H 5 N4, Canada ; ECOGENE-21 and Lipid Clinic, Chicoutimi Hospital, 305 rue St-Vallier, Saguenay, Québec G7H5H6, Canada.
authors.forename: Luigi
authors.initials: L
authors.lastname: Bouchard
keywords: ATP-binding cassette transporter A1; Aging; Cardiovascular disease; Epigenetics
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