Abstract
BackgroundPrevious 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.ResultsABCA1 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.ConclusionsThis 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.
Highlights
Previous studies have suggested that DNA methylation contributes to coronary artery disease (CAD) risk variability
We have recently shown that a higher DNA methylation level at the ATP-binding cassette transporter A1 (ABCA1) gene promoter locus was associated with lower high-density lipoprotein cholesterol (HDL-C) levels and a previous history of CAD in familial hypercholesterolemia (FH) [7]
We first assessed whether mean DNA methylation levels at 8 CpG dinucleotides located at the ABCA1 gene promoter locus might be associated with CAD occurrence and aging in men (Figure 1)
Summary
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. The ATP-binding cassette transporter A1 (ABCA1) catalyzes the transfer of lipids from various tissues and cells to apolipoprotein A1 containing lipoproteins [1] This reaction is the rate-limiting step in the biogenesis of high-density lipoprotein particles and reverse cholesterol transport [1]. Our group and others have shown that higher ABCA1 DNA methylation levels were associated with a lower ABCA1 gene expression [14,15] All these previous results suggest that perturbations of the ABCA1 epigenetic profile might be a new molecular mechanism involved in CAD.
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