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Acetylsalicylic acid, aging and coronary artery disease are associated with ABCA1 DNA methylation in men.

Guay SP, Légaré C, Houde AA, Mathieu P, Bossé Y, Bouchard L - Clin Epigenetics (2014)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Interaction between coronary artery disease and aging on ABCA1 DNA methylation levels in leucocytes. Older men (>61 years old) with coronary artery disease (CAD) had the highest mean ATP-binding cassette transporter A1 (ABCA1) DNA methylation levels. CAD occurrence and aging interact to increase ABCA1 DNA methylation levels in leucocytes (P = 0.01). P-values were obtained after consideration of acetylsalicylic acid treatment.
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Figure 2: Interaction between coronary artery disease and aging on ABCA1 DNA methylation levels in leucocytes. Older men (>61 years old) with coronary artery disease (CAD) had the highest mean ATP-binding cassette transporter A1 (ABCA1) DNA methylation levels. CAD occurrence and aging interact to increase ABCA1 DNA methylation levels in leucocytes (P = 0.01). P-values were obtained after consideration of acetylsalicylic acid treatment.

Mentions: Interestingly, we also observed a significant interaction between CAD status and age on mean ABCA1 DNA methylation levels (P = 0.01; Figure 2). Older men with CAD (age ≥61 years old; n = 19) showed significantly higher DNA methylation levels at the ABCA1 gene promoter locus compared to younger men without CAD (age <61 years old), older men without CAD (age ≥61 years old) and younger men with CAD (age <61 years old) (Table 1 and Figure 2), independently of current treatment. No significant mean ABCA1 DNA methylation level difference was observed between younger men with or without CAD (P = 0.67). In older men (age ≥61 years old), we also observed that a higher ABCA1 DNA methylation level was positively correlated with total cholesterol (r = 0.34; P = 0.03), low-density lipoprotein cholesterol (r = 0.32; P = 0.04), as well with fasting triglyceride levels (trend; r = 0.26; P = 0.09) after consideration of age, CAD status and medication. In younger men (age <61 years old), no significant association was observed between mean ABCA1 DNA methylation levels and plasma lipid profile (data not shown).


Acetylsalicylic acid, aging and coronary artery disease are associated with ABCA1 DNA methylation in men.

Guay SP, Légaré C, Houde AA, Mathieu P, Bossé Y, Bouchard L - Clin Epigenetics (2014)

Interaction between coronary artery disease and aging on ABCA1 DNA methylation levels in leucocytes. Older men (>61 years old) with coronary artery disease (CAD) had the highest mean ATP-binding cassette transporter A1 (ABCA1) DNA methylation levels. CAD occurrence and aging interact to increase ABCA1 DNA methylation levels in leucocytes (P = 0.01). P-values were obtained after consideration of acetylsalicylic acid treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4120725&req=5

Figure 2: Interaction between coronary artery disease and aging on ABCA1 DNA methylation levels in leucocytes. Older men (>61 years old) with coronary artery disease (CAD) had the highest mean ATP-binding cassette transporter A1 (ABCA1) DNA methylation levels. CAD occurrence and aging interact to increase ABCA1 DNA methylation levels in leucocytes (P = 0.01). P-values were obtained after consideration of acetylsalicylic acid treatment.
Mentions: Interestingly, we also observed a significant interaction between CAD status and age on mean ABCA1 DNA methylation levels (P = 0.01; Figure 2). Older men with CAD (age ≥61 years old; n = 19) showed significantly higher DNA methylation levels at the ABCA1 gene promoter locus compared to younger men without CAD (age <61 years old), older men without CAD (age ≥61 years old) and younger men with CAD (age <61 years old) (Table 1 and Figure 2), independently of current treatment. No significant mean ABCA1 DNA methylation level difference was observed between younger men with or without CAD (P = 0.67). In older men (age ≥61 years old), we also observed that a higher ABCA1 DNA methylation level was positively correlated with total cholesterol (r = 0.34; P = 0.03), low-density lipoprotein cholesterol (r = 0.32; P = 0.04), as well with fasting triglyceride levels (trend; r = 0.26; P = 0.09) after consideration of age, CAD status and medication. In younger men (age <61 years old), no significant association was observed between mean ABCA1 DNA methylation levels and plasma lipid profile (data not shown).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus