New cardiovascular disease markers in patients with familial hypercholesterolemia carriers of genetic variants.

Objectives: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by elevated levels of low-density lipoprotein cholesterol (LDLc). The early diagnosis of FH can reduce unfavorable outcomes in this population, but genetic study is not available in all populations. This study aimed to evaluate new cardiovascular plasma markers (GDF-15, CXCL16, FABP3, FABP4, LIGHT, sCD14, ucMGP), as well as Lp(a) levels, in individuals genetically characterized for FH, classified according to treatment with statins.

Generation and validation of a classification model to diagnose familial hypercholesterolaemia in adults.

Background And Aims: The early diagnosis of familial hypercholesterolaemia is associated with a significant reduction in cardiovascular disease (CVD) risk. While the recent use of statistical and machine learning algorithms has shown promising results in comparison with traditional clinical criteria, when applied to screening of potential FH cases in large cohorts, most studies in this field are developed using a single cohort of patients, which may hamper the application of such algorithms to other populations. In the current study, a logistic regression (LR) based algorithm was developed combining observations from three different national FH cohorts, from Portugal, Brazil and Sweden.

Identification of pathogenic variants in the Brazilian cohort with Familial hypercholesterolemia using exon-targeted gene sequencing.

Familial hypercholesterolemia (FH) is a monogenic disease characterized by high plasma low-density lipoprotein cholesterol (LDL-c) levels and increased risk of premature atherosclerotic cardiovascular disease. Mutations in FH-related genes account for 40% of FH cases worldwide. In this study, we aimed to assess the pathogenic variants in FH-related genes in the Brazilian FH cohort FHBGEP using exon-targeted gene sequencing (ETGS) strategy.

Polygenic risk score for hypercholesterolemia in a Brazilian familial hypercholesterolemia cohort.

Background And Aims: Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of LDL-C leading to premature cardiovascular disease (CAD). Only about 40% of individuals with a clinical diagnosis of FH have a causative genetic variant identified, and a proportion of genetically negative cases may have a polygenic cause rather than a still unidentified monogenic cause. This work aims to evaluate and validate the role of a polygenic risk score (PRS) associated with hypercholesterolemia in a Brazilian FH cohort and its clinical implications.

Effects of PCSK9 missense variants on molecular conformation and biological activity in transfected HEK293FT cells.

PCSK9 gain-of-function (GOF) variants increase degradation of low-density lipoprotein receptor (LDLR) and are potentially associated with Familial Hypercholesterolemia (FH). This study aimed to explore the effects of PCSK9 missense variants on protein structure and interactions with LDLR using molecular modeling analyses and in vitro functional studies. Variants in FH-related genes were identified in a Brazilian FH cohort using an exon-target gene sequencing strategy.

In silico analysis of upstream variants in Brazilian patients with Familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is a prevalent autosomal genetic disease associated with increased risk of early cardiovascular events and death due to chronic exposure to very high levels of low-density lipoprotein cholesterol (LDL-c). Pathogenic variants in the coding regions of LDLR, APOB and PCSK9 account for most FH cases, and variants in non-coding regions maybe involved in FH as well. Variants in the upstream region of LDLR, APOB and PCSK9 were screened by targeted next-generation sequencing and their effects were explored using in silico tools.

Screening of and Genes for Sitosterolemia in a Familial Hypercholesterolemia Cascade Screening Program.

Background: Sitosterolemia is a rare autosomal recessive disorder caused by homozygous or compound heterozygous variants in . The disease is characterized by increased plasma plant sterols. Small case series suggest that patients with sitosterolemia have wide phenotypic heterogeneity with great variability on either plasma cholesterol levels or development of atherosclerotic cardiovascular disease.

[Identification of genetic variants associated with familial hypercholesterolemia in Chilean children and adolescents].

Background: Familial hypercholesterolemia (FH) is commonly associated with mutations in-LDL receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9).

Aim: To identify genetic variants associated with FH in a population of children and adolescents with hypercholesterolemia or a family history of-demonstrated early CVD.

Material And Methods: Clinical and biochemical parameters were evaluated, and nine genes related to FH were sequenced namely LDLR, APOB, PCSK9, LDLRAP1, LIPA, APOE, ABCG5, ABCG8 and STAP1, in 55 children and adolescents aged 1 to 18 years old, from non-consanguineous families.

Screening for Familial Hypercholesterolemia in Small Towns: Experience from 11 Brazilian Towns in the Hipercolbrasil Program.

Background: Familial hypercholesterolemia (FH) is a genetic disease characterized by elevated serum levels of low-density lipoprotein cholesterol (LDL-C), and it is associated with the occurrence of early cardiovascular disease. In Brazil, HipercolBrasil, which is currently the largest FH cascade screening program, has already identified more than 2000 individuals with causal genetic variants for FH. The standard approach is based on cascade screening of referred index cases, individuals with hypercholesterolemia and clinical suspicion of FH.

Cascade screening and genetic diagnosis of familial hypercholesterolemia in clusters of the Southeastern region from Brazil.

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by high levels of low-density lipoprotein-cholesterol (LDLc), associated to premature cardiovascular disease. The detection of the variants related to FH is important to improve the early diagnosis in probands / index-cases (ICs) and their relatives. We included ICs with FH and their relatives, living in a small region of Minas Gerais state-Brazil, which were classified according to Dutch Lipid Clinic Network Criteria (DLCNC) and submitted to sequencing of genes related to FH (LDLR, APOB, PCSK9, LDLRAP1, LIPA, STAP1, APOE, ABCG5 e ABCG8).

Genomics, epigenomics and pharmacogenomics of familial hypercholesterolemia (FHBGEP): A study protocol.

Background: Familial hypercholesterolemia (FH) is a genetic disease that affects millions of people worldwide.

Objectives: The study protocol FHBGEP was design to investigate the main genomic, epigenomic, and pharmacogenomic factors associated with FH and polygenic hypercholesterolemia (PH).

Methods: FH patients will be enrolled at six research centers in Brazil.

Predictors of Family Enrollment in a Genetic Cascade Screening Program for Familial Hypercholesterolemia.

Background: Genetic cascade screening is the most cost-effective method for the identification of individuals with familial hypercholesterolemia (FH), but the best strategies for the enrollment of at-risk individuals in a FH screening program are not fully known.

Objective: The aim of this study is to identify the best predictors of familial enrollment into genetic screening, using features derived from tested probands.

Methods: One hundred and eighty-three index-cases (ICs) with a positive genetic result that had relatives screened from 01/2011 to 07/2015 were included.

Limited Ca2+ and PKA-pathway dependent neurogenic differentiation of human adult mesenchymal stem cells as compared to fetal neuronal stem cells.

The ability of mesenchymal stem cells to generate functional neurons in culture is still a matter of controversy. In order to assess this issue, we performed a functional comparison between neuronal differentiation of human MSCs and fetal-derived neural stem cells (NSCs) based on morphological, immunocytochemical, and electrophysiological criteria. Furthermore, possible biochemical mechanisms involved in this process were presented.