RESUMEN
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.
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Asunto(s)
Metilación de ADN , Hiperlipoproteinemia Tipo II , Proteína Asociada a Proteínas Relacionadas con Receptor de LDL , Proproteína Convertasa 9 , Receptores de LDL , Humanos , Proproteína Convertasa 9/genética , Receptores de LDL/genética , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/sangre , Masculino , Femenino , Persona de Mediana Edad , Adulto , Proteína Asociada a Proteínas Relacionadas con Receptor de LDL/genética , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/etiología , Islas de CpG , Proteínas Adaptadoras Transductoras de SeñalesRESUMEN
Aim: This study investigated the influence of antidepressant drugs on methylation status of KCNE1, KCNH2 and SCN5A promoters and ECG parameters in adult psychiatric patients. Materials & methods: Electrocardiographic evaluation (24 h) and blood samples were obtained from 34 psychiatric patients before and after 30 days of antidepressant therapy. Methylation of promoter CpG sites of KCNE1, KCNH2 and SCN5A was analyzed by pyrosequencing. Results: Three CpG and four CpG sites of KCNE1 and SCN5A, respectively, had increased % methylation after treatment. Principal component analysis showed correlations of the methylation status with electrocardiographic variables, antidepressant doses and patient age. Conclusion: Short-term treatment with antidepressant drugs increase DNA methylation in KCNE1 and SCN5A promoters, which may induce ECG alterations in psychiatric patients.