Bourbon Mafalda, Alves Ana Catarina, Alonso Rodrigo, Mata Nelva, Aguiar Pedro, Padró Teresa, Mata Pedro
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.
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.
Atherosclerosis. 2017 Jul;262:8-13. doi: 10.1016/j.atherosclerosis.2017.04.002. Epub 2017 Apr 6.
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.
The study recruited 2938 individuals with genetic diagnosis of FH belonging to 775 families. Statistical analysis was performed using SPSS v23.
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).
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.
家族性高胆固醇血症（FH）是一种常染色体显性胆固醇代谢疾病，会增加早发性动脉粥样硬化性心血管疾病（ASCVD）的风险。因此，对这些患者进行早期识别和治疗可改善预后并减轻心血管疾病死亡率负担。这项研究的目的是对SAFEHEART（西班牙家族性高胆固醇血症队列研究）登记处进行突变分析。
该研究招募了来自775个家庭的2938名经基因诊断为FH的个体。使用SPSS v23进行统计分析。
本研究共检测到194个变异，其中24个此前从未被描述过。约88%的患者有一个致病或可能致病的变异。无功能变异的患者比有缺陷变异的患者具有更严重的表型，其致动脉粥样硬化颗粒（总胆固醇、低密度脂蛋白胆固醇和载脂蛋白B）水平显著更高。
本研究展示了SAFEHEART登记处纳入的FH患者的分子特征及其与表型表达的关系。大多数基因变异被认为是致病或可能致病 的，这为使用该登记处对FH患者的预后、治疗和生存进行的录入及随访数据分析提供了高度的可信度。
