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

Silva Rodrigues Marçal, Elisangela da; Borges, Jéssica Bassani; Bastos, Gisele Medeiros; Crespo Hirata, Thiago Dominguez; de Oliveira, Victor Fernandes; Gonçalves, Rodrigo Marques; Faludi, Andre Arpad; Dias França, João Italo; de Oliveira Silva, Daiana Vitor; Malaquias, Vanessa Barbosa; Luchessi, Andre Ducati; Silbiger, Vivian Nogueira; Nakazone, Marcelo Arruda; Carmo, Tayanne Silva; Silva Souza, Dorotéia Rossi; Sampaio, Marcelo Ferraz; Crespo Hirata, Rosario Dominguez; Hirata, Mario Hiroyuki

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

Silva Rodrigues Marçal, Elisangela da; Borges, Jéssica Bassani; Bastos, Gisele Medeiros; Crespo Hirata, Thiago Dominguez; de Oliveira, Victor Fernandes; Gonçalves, Rodrigo Marques; Faludi, Andre Arpad; Dias França, João Italo; de Oliveira Silva, Daiana Vitor; Malaquias, Vanessa Barbosa; Luchessi, Andre Ducati; Silbiger, Vivian Nogueira; Nakazone, Marcelo Arruda; Carmo, Tayanne Silva; Silva Souza, Dorotéia Rossi; Sampaio, Marcelo Ferraz; Crespo Hirata, Rosario Dominguez; Hirata, Mario Hiroyuki.

Afiliación

Silva Rodrigues Marçal ED; Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, 05508-000, Brazil.
Borges JB; Laboratory of Molecular Research in Cardiology, Institute of Cardiology Dante Pazzanese, Sao Paulo, 04012-909, Brazil.
Bastos GM; Department of Research, Hospital Beneficiencia Portuguesa de Sao Paulo, Sao Paulo, 01323-001, Brazil.
Crespo Hirata TD; Department of Research, Hospital Beneficiencia Portuguesa de Sao Paulo, Sao Paulo, 01323-001, Brazil.
de Oliveira VF; Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, 05508-000, Brazil.
Gonçalves RM; Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, 05508-000, Brazil.
Faludi AA; Medical Clinic Division, Institute of Cardiology Dante Pazzanese, Sao Paulo, 04012-909, Brazil.
Dias França JI; Medical Clinic Division, Institute of Cardiology Dante Pazzanese, Sao Paulo, 04012-909, Brazil.
de Oliveira Silva DV; Center for Clinical Trials & Pharmacovigilance, Butantan Institute, Sao Paulo, 05585-000, Brazil.
Malaquias VB; Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, 05508-000, Brazil.
Luchessi AD; Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, 05508-000, Brazil.
Silbiger VN; Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, 59012-570, Brazil.
Nakazone MA; Graduate Program in Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, 59012-570, Brazil.
Carmo TS; Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, 59012-570, Brazil.
Silva Souza DR; Graduate Program in Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, 59012-570, Brazil.
Sampaio MF; Department of Cardiology & Cardiovascular Surgery, Sao Jose do Rio Preto Medical School, Sao Jose do Rio Preto, 15090-000, Brazil.
Crespo Hirata RD; Department of Biochemistry & Molecular Biology, Sao Jose do Rio Preto Medical School, Sao Jose do Rio Preto, 15090-000, Brazil.
Hirata MH; Department of Biochemistry & Molecular Biology, Sao Jose do Rio Preto Medical School, Sao Jose do Rio Preto, 15090-000, Brazil.

Epigenomics ; : 1-12, 2024 Jun 17.

Article en En | MEDLINE | ID: mdl-38884343

ABSTRACT

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.

[Box see text].

Palabras clave

DNA methylation; LDLR; LDLRAP1; PCSK9; cardiovascular events; epigenomics; familial hypercholesterolemia

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