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DNA methylation variations at CETP and LPL gene promoter loci: New molecular biomarkers associated with blood lipid profile variability

      Highlights

      • In men, CETP DNA methylation is associated with HDL and triglycerides levels.
      • CETP DNA methylation is associated with LDL-C levels.
      • CETP mass is correlated with LDL particle phenotype.
      • LPL DNA methylation is associated with HDL size, HDL-C and triglyceride levels.
      • Gene specific DNA methylation contributes to explain 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.

      Methods and 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.

      Conclusion

      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.

      Keywords

      List of abbreviations:

      ABCA1 (ATP-binding cassette A1), apoA1 (apolipoprotein A1), apoB (apolipoproprotein B), APOE (apolipoprotein E), AU (arbitrary unit), BMI (body mass index), CAD (coronary artery disease), CE (cholesteryl esters), CETP (cholesteryl ester transfer protein), CVD (cardiovascular disease), GAPDH (Glyceraldehyde 3-phosphate dehydrogenase), FH (familial hypercholesterolaemia), HDL-C (high-density lipoprotein cholesterol), LCAT (lecithin-cholesterol acyltransferase), LDL-C (low-density lipoprotein cholesterol), LDLR (low-density lipoprotein receptor), LPL (lipoprotein lipase), PCR (polymerase chain reaction), PL (phospholipids), RIN (RNA integrity number), SLSJ (Saguenay-Lac-Saint-Jean), TC (total cholesterol), TG (triglyceride), VAT (visceral adipose tissue), VLDL (very low-density lipoprotein)
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