Mafalda Bourbon1, Ana Catarina Alves2, Rodrigo Alonso3, Nelva Mata4, Pedro Aguiar5, Teresa Padró6, Pedro Mata7. 1. Unidade de I&D, Grupo de Investigação Cardiovascular, Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal; BioISI - Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal. Electronic address: mafalda.bourbon@insa.min-saude.pt. 2. Unidade de I&D, Grupo de Investigação Cardiovascular, Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal; BioISI - Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal. 3. Fundación Hipercolesterolemia Familiar, Madrid, Spain; Clínica las Condes, Santiago de Chile, Chile. 4. Fundación Hipercolesterolemia Familiar, Madrid, Spain; Department of Epidemiology, Madrid Health Authority, Madrid, Spain. 5. Centro de Investigação de Saúde Pública, Escola Nacional de Saúde Pública, Universidade Nova de Lisboa, Portugal. 6. Instituto Catalán Ciencias Cardiovasculares, IIB-Sant Pau, Barcelona, Spain. 7. Fundación Hipercolesterolemia Familiar, Madrid, Spain.
Abstract
BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is an autosomal dominant disease of cholesterol metabolism that confers an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Therefore, early identification and treatment of these patients can improve prognosis and reduce the burden of cardiovascular mortality. The aim of this work was to perform the mutational analysis of the SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) registry. METHODS: The study recruited 2938 individuals with genetic diagnosis of FH belonging to 775 families. Statistical analysis was performed using SPSS v23. RESULTS: A total of 194 variants have been detected in this study, 24 of them were never described before. About 88% of the patients have a pathogenic or likely pathogenic variant. Patients with null variants have a more severe phenotype than patients with defective variants, presenting with significantly higher levels of atherogenic particles (total cholesterol, LDL-cholesterol and apolipoprotein B). CONCLUSIONS: This study shows the molecular characteristics of the FH patients included in the SAFEHEART registry and the relationship with the phenotypic expression. The majority of the genetic variants are considered to be pathogenic or likely pathogenic, which confers a high level of confidence to the entry and follow-up data analysis performed with this registry concerning FH patients' prognosis, treatment and survival.
BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is an autosomal dominant disease of cholesterol metabolism that confers an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Therefore, early identification and treatment of these patients can improve prognosis and reduce the burden of cardiovascular mortality. The aim of this work was to perform the mutational analysis of the SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) registry. METHODS: The study recruited 2938 individuals with genetic diagnosis of FH belonging to 775 families. Statistical analysis was performed using SPSS v23. RESULTS: A total of 194 variants have been detected in this study, 24 of them were never described before. About 88% of the patients have a pathogenic or likely pathogenic variant. Patients with null variants have a more severe phenotype than patients with defective variants, presenting with significantly higher levels of atherogenic particles (total cholesterol, LDL-cholesterol and apolipoprotein B). CONCLUSIONS: This study shows the molecular characteristics of the FH patients included in the SAFEHEART registry and the relationship with the phenotypic expression. The majority of the genetic variants are considered to be pathogenic or likely pathogenic, which confers a high level of confidence to the entry and follow-up data analysis performed with this registry concerning FH patients' prognosis, treatment and survival.
Authors: Marta Gazzotti; Manuela Casula; Stefano Bertolini; Maria Elena Capra; Elena Olmastroni; Alberico Luigi Catapano; Cristina Pederiva Journal: Front Genet Date: 2022-06-20 Impact factor: 4.772