Genetics
CETP gene promoter methylation correlates with LDL-C, HDL-C, and HDL particle size in familial hypercholesterolaemia patients (Atherosclerosis 2013)
Original title: DNA methylation variations at CETP and LPL gene promoter loci: new molecular biomarkers associated with blood lipid profile variability
Researchers analyzed leucocyte DNA methylation at the LDLR, CETP, LCAT, and LPL gene promoters in ninety-eight untreated familial hypercholesterolaemia patients to test whether epigenetic marks track with blood lipid profile. In both sexes, CETP DNA methylation was negatively associated with LDL cholesterol (r < -0.32; p < 0.05). In men specifically, CETP methylation was also associated with HDL cholesterol (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). LPL methylation correlated with HDL-C (r = 0.22; p = 0.031) and HDL particle size (r = 0.47; p = 0.013), and its association with HDL-C and LPL mRNA levels was confirmed in visceral adipose tissue from 30 men with severe obesity. The authors conclude that CETP and LPL DNA methylation are linked to blood lipid profile, supporting epigenetics as a contributor to the molecular basis of dyslipidemia.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.