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

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.