Methylation status of LDLR , PCSK9 and LDLRAP1 is associated with cardiovascular events in familial hypercholesterolemia.
Elisangela da Silva Rodrigues MarçalJessica Bassani BorgesGisele Medeiros BastosThiago Dominguez Crespo HirataVictor Fernandes OliveiraRodrigo Marques GonçalvesAndre Arpad FaludiJoão Italo Dias FrançaDaiana Vitor de Oliveira SilvaVanessa Barbosa MalaquiasAndre Ducati LuchessiVivian Nogueira SilbigerMarcelo Arruda NakazoneTayanne Silva CarmoDorotéia Rossi Silva SouzaMarcelo Ferraz SampaioRosario Dominguez Crespo HirataMario Hiroyuki HirataPublished in: Epigenomics (2024)
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.