Methylation status of LDLR, PCSK9 and LDLRAP1 is associated with cardiovascular events in familial hypercholesterolemia

Epigenomics. 2024;16(11-12):809-820. doi: 10.1080/17501911.2024.2351792. Epub 2024 Jun 17.

Abstract

Aim: Methylation of LDLR, PCSK9 and LDLRAP1 CpG sites was assessed in patients with familial hypercholesterolemia (FH). Methods: DNA methylation of was analyzed by pyrosequencing in 131 FH patients and 23 normolipidemic (NL) subjects.Results: LDLR, PCSK9 and LDLRP1 methylation was similar between FH patients positive (MD) and negative (non-MD) for pathogenic variants in FH-related genes. LDLR and PCSK9 methylation was higher in MD and non-MD groups than NL subjects (p < 0.05). LDLR, PCSK9 and LDLRAP1 methylation profiles were associated with clinical manifestations and cardiovascular events in FH patients (p < 0.05).Conclusion: Differential methylation of LDLR, PCSK9 and LDLRAP1 is associated with hypercholesterolemia and cardiovascular events. This methylation profile maybe useful as a biomarker and contribute to the management of FH.

Keywords: DNA methylation; LDLR; LDLRAP1; PCSK9; cardiovascular events; epigenomics; familial hypercholesterolemia.

Plain language summary

[Box: see text].

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / genetics
  • CpG Islands
  • DNA Methylation*
  • Female
  • Humans
  • Hyperlipoproteinemia Type II* / blood
  • Hyperlipoproteinemia Type II* / genetics
  • LDL-Receptor Related Protein-Associated Protein* / genetics
  • Male
  • Middle Aged
  • Proprotein Convertase 9* / genetics
  • Receptors, LDL* / genetics

Substances

  • Proprotein Convertase 9
  • Receptors, LDL
  • PCSK9 protein, human
  • LDLRAP1 protein, human
  • LDLR protein, human
  • LDL-Receptor Related Protein-Associated Protein
  • Adaptor Proteins, Signal Transducing