Document Detail

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    
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.
Simon-Pierre Guay; Diane Brisson; Johannie Munger; Benoit Lamarche; Daniel Gaudet; Luigi Bouchard
Related Documents :
7633946 - Retroviral transfer of hsv1-tk gene into human lung cancer cell line.
8835216 - Preclinical studies of lymphocyte gene therapy for mild hunter syndrome (mucopolysaccha...
10074136 - Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of...
12208136 - Comparison of epidermal keratinocytes and dermal fibroblasts as potential target cells ...
21262966 - Tubulin tyrosine ligase-like genes ttll3 and ttll6 maintain zebrafish cilia structure a...
8030286 - The human papillomavirus type 16 e5 gene cooperates with the e7 gene to stimulate proli...
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:  -    
ECOGENE-1 and Lipid Clinic; Chicoutimi Hospital; Saguenay, QC Canada; Department of Biochemistry; Université de Sherbrooke; Sherbrooke, QC Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Use of multilocus methylation-specific single nucleotide primer extension (MS-SNuPE) technology in d...
Next Document:  Prenatal antiepileptic exposure associates with neonatal DNA methylation differences.