title: DNA methylation variations at CETP and LPL gene promoter loci: new molecular biomarkers associated with blood lipid profile variability.
abstract: BACKGROUND
  Recent findings suggest that DNA methylation, a well-known epigenetic mechanism, is involved in high-density lipoprotein cholesterol (HDL-C) metabolism and increased cardiovascular disease risk. The aim of this study was thus to assess whether DNA methylation within key genes of lipoprotein metabolism is associated with blood lipid profile variability.
  
  
  RESULTS
  Ninety-eight untreated familial hypercholesterolaemia patients (61 men and 37 women) were recruited for leucocyte DNA methylation analyses at the LDLR, CETP, LCAT and LPL gene promoter loci using bisulfite pyrosequencing. LPL DNA methylation was correlated with HDL-C (r = 0.22; p = 0.031) and HDL particle size (r = 0.47, p = 0.013). In both sex, CETP DNA methylation was negatively associated with low-density lipoprotein cholesterol levels (r < -0.32; p < 0.05). In men, CETP DNA methylation was associated with HDL-C (r = -0.36; p = 0.006), HDL-triglyceride levels (r = 0.59; p < 0.001) and HDL particle size (r = -0.44, p = 0.019). In visceral adipose tissue from 30 men with severe obesity, the associations between LPL DNA methylation, HDL-C (r = -0.40; p = 0.03) and LPL mRNA levels (r = -0.61, p < 0.001) were confirmed.
  
  
  CONCLUSIONS
  CETP and LPL DNA methylation levels are associated with blood lipid profile, suggesting that further studies of epipolymorphisms should most certainly contribute to a better understanding of the molecular bases of dyslipidemia.
authors.affiliation: Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada. simon-pierre.guay@usherbrooke.ca
authors.forename: S P
authors.initials: SP
authors.lastname: Guay
authors.forename: D
authors.initials: D
authors.lastname: Brisson
authors.forename: B
authors.initials: B
authors.lastname: Lamarche
authors.forename: P
authors.initials: P
authors.lastname: Marceau
authors.forename: M C
authors.initials: MC
authors.lastname: Vohl
authors.forename: D
authors.initials: D
authors.lastname: Gaudet
authors.forename: L
authors.initials: L
authors.lastname: Bouchard
mesh_terms: D000328:Adult; D016009:Chi-Square Distribution; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000201:enzymology / Q000235:genetics*; D016014:Linear Models; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood / Q000201:enzymology / Q000235:genetics; D010641:Phenotype; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011973:Receptors, LDL / Q000235:genetics; D015203:Reproducibility of Results; D012307:Risk Factors; D017422:Sequence Analysis, DNA / Q000379:methods; D012737:Sex Factors
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D005819:Genetic Markers; C573412:LDLR protein, human; D008055:Lipids; D011973:Receptors, LDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; C548261:LPL protein, human; D008071:Lipoprotein Lipase