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ABCA1 gene promoter DNA methylation is associated with HDL particle profile and coronary artery disease in familial hypercholesterolemia.
MedLine Citation:
PMID:  22419126     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
High-density lipoproteins cholesterol (HDL-C), a strong coronary artery disease (CAD) clinical biomarker, shows significant interindividual variability. However, the molecular mechanisms involved remain mostly unknown. ATP-binding cassette A1 (ABCA1) catalyzes the cholesterol transfer from peripheral cells to nascent HDL particles. Recently, a differentially methylation region was identified in ABCA1 gene promoter locus, near the first exon. Therefore, we hypothesized that DNA methylation changes at ABCA1 gene locus is one of the molecular mechanisms involved in HDL-C interindividual variability. The study was conducted in familial hypercholesterolemia (FH), a monogenic disorder associated with a high risk of CAD . Ninety-seven FH patients (all p.W66G for the LDLR gene mutation and not under lipid-lowering treatment) were recruited and finely phenotyped for DNA methylation analyses at ABCA1 gene locus. ABCA1 DNA methylation levels were found negatively correlated with circulating HDL-C (r = -0.20; p = 0.05), HDL2-phospholipid levels (r = -0.43; p = 0.04), and with a trend for association with HDL peak particle size (r = -0.38; p = 0.08). ABCA1 DNA methylation levels were also found associated with prior history of CAD (CAD = 40.2% vs. without CAD = 34.3%; p = 0.003). These results suggest that epigenetic changes within the ABCA1 gene promoter contribute to the interindividual variability in plasma HDL-C concentrations and are associated with CAD expression. These findings could change our understanding of the molecular mechanisms involved in the pathophysiological processes leading to CAD.
Authors:
Simon-Pierre Guay; Diane Brisson; Johannie Munger; Benoit Lamarche; Daniel Gaudet; Luigi Bouchard
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-01
Journal Detail:
Title:  Epigenetics : official journal of the DNA Methylation Society     Volume:  7     ISSN:  1559-2308     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-3-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101265293     Medline TA:  Epigenetics     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
ECOGENE-1 and Lipid Clinic; Chicoutimi Hospital; Saguenay, QC Canada; Department of Biochemistry; Université de Sherbrooke; Sherbrooke, QC Canada.
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