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Background   HMGCR, SCAP, SREBF1, SREBF2  and  TBL2  are well-known genes that are involved in the process of lipid metabolism. However, it is not known whether epigenetic changes of these genes are associated with lipid metabolism. In this study, the methylation levels of the  HMGCR, SCAP, SREBF1, SREBF2  and  TBL2  genes were analyzed between samples from a hyper-low-density lipoprotein cholesterolemia (hyper-LDL) group and a control group to examine the association between the methylation levels of these genes and the risk of hyper-LDL.    Methods  In this study, a case-control approach was used to explore the association between DNA methylation and hyper-LDL. The DNA methylation levels of  HMGCR, SCAP, SREBF1, SREBF2  and  TBL2  genes and 231 CpG sites in the promoter regions of these genes were measured in 98 hyper-LDL participants and 89 participants without hypo-LDL.    Results  Compared with participants without hyper-LDL, patients with hyper-LDL  TBL2  gene had lower methylation levels (11.93 vs. 12.02,  P  = 0.004). The methylation haplotypes with significant abundance in the TBL2 gene are tc ( P  = 0.034), ccct ( P  = 0.025), ctctttctttt ( P  = 0.040), cc ( P  = 0.028), and tc.    Conclusion  The study demonstrates that participants with hyper-LDL have lower methylation of  TBL2 . The results suggest that DNA methylation of  TBL2  can decrease the risk for hyper-LDL in humans.

TBL2 methylation is associated with hyper-low-density lipoprotein cholesterolemia: a case-control study