title: Epigenome-wide analysis in familial hypercholesterolemia identified new loci associated with high-density lipoprotein cholesterol concentration.
abstract: OBJECTIVE
  This study aims to assess whether epigenetic changes may account for high-density lipoprotein cholesterol (HDL-C) level variability in familial hypercholesterolemia (FH), a recognized human model to study cardiovascular disease risk modulators.
  
  
  METHODS
  A genome-wide DNA methylation analysis (Infinium HumanMethylation27 BeadChip, Illumina) was performed on peripheral blood DNA samples obtained from men with FH with low (n = 10) or high (n = 11) HDL-C concentrations. The initial association with one of the top differentially methylated loci located in the promoter of the TNNT1 gene was replicated in a cohort of 276 FH subjects using pyrosequencing.
  
  
  RESULTS
  According to the Ingenuity Pathway Analysis software, the HDL-C differentially methylated loci identified were significantly associated with pathways related to lipid metabolism and cardiovascular disease. TNNT1 DNA methylation levels were positively correlated with mean HDL particle size, HDL-phospholipid, HDL-apolipoprotein AI, HDL-C and TNNT1 expression levels.
  
  
  CONCLUSIONS
  These results suggest that epigenome-wide changes account for interindividual variations in HDL particle metabolism and that TNNT1 is a new candidate gene for dyslipidemia.
authors.affiliation: Department of Biochemistry, Université de Sherbrooke, 225 St-Vallier Street, Chicoutimi, QC, G7H 7P2, Canada.
authors.forename: Simon-Pierre
authors.initials: SP
authors.lastname: Guay
authors.forename: Gregory
authors.initials: G
authors.lastname: Voisin
authors.forename: Diane
authors.initials: D
authors.lastname: Brisson
authors.forename: Johannie
authors.initials: J
authors.lastname: Munger
authors.forename: Benoît
authors.initials: B
authors.lastname: Lamarche
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.forename: Luigi
authors.initials: L
authors.lastname: Bouchard
mesh_terms: D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics*; D015331:Cohort Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics*; D050356:Lipid Metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D020107:Troponin T / Q000235:genetics* / Q000378:metabolism
chemical_list: D008076:Cholesterol, HDL; D012333:RNA, Messenger; D020107:Troponin T