Diabetic vascular disease and Maturity-onset diabetes of the young

Aim: Vascular disease such as cardiovascular and cerebrovascular diseases, or retinopathy, nephropathy and neuropathy are common in diabetes. Maturity - onset diabetes of the young (MODY) describes a clinically heterogeneous group of familial diabetes characterized by monogenic, autosomal dominant inheritance that generally results from beta cell dysfunction. This study aims to assess the presence of vascular complications on Portuguese patients with a clinical diagnosis of MODY.

Looks Like FH But it’s not FH: Extended Lipid Profile of Paediatric Clinical FH Patients Reveals a Different Lipid Profile in FH Negative Patients

Aim: Familial Hypercholesterolemia (FH) is a common autosomal dominant disorder, caused by mutations in genes involved in cholesterol’s clearance (LDLR, APOB, PCSK 9). Clinical diagnosis is usually based on high total cholesterol or LDL-C levels and family history of premature coronary heart disease. Using an extended lipid profile of paediatric dyslipidemic patients, we aim to identify biomarkers for a better diagnosis of FH in clinical settings.

Will Familial Hypercholesterolaemia Cohorts Hide Many More Lisosomal Acid Lipase Deficiency Patients?

Aims: Lisosomal Acid Lipase Deficiency (LALD), historical known as Cholesterol Ester Storage Disease (CESD), is an autosomal lisosomal storage recessive disorder and an unrecognized cause of dyslipidaemia. Mutations in LIPA gene are the underlying cause of LALD, being a mutation in the splice site of exon 8 the most common cause of the disease. Patients with LALD present dyslipidaemia and altered liver function. The aim of this work was to analyze LIPA gene in patients with unexplained dyslipidaemia.

Functionally characterization of the most common LDLR missense alterations found in Portuguese FH patients

Aims: Mutations in the LDLR gene are the major cause of familial hypercholesterolaemia (FH), which results in defective catabolism of LDL leading to premature coronary heart disease. Presently, more than 1700 different mutations in the LDLR gene have been described as causing FH but the majority of them remain without functional characterization. In the Portuguese Familial Hypercholesterolemia Study (PFHS), 123 LDLR alterations were found in 243 index patients and their relatives up to date. Until now, 70 of these alterations already have a final classification of pathogenic and 15 have been proved by in vitro studies to be non-pathogenic. The aim of the present work is to functionally characterize 16 LDLR missense alterations found in Portuguese FH patients and worldwide.

Construction of a New Familial Hypercholesterolemia Variant Data Base. A Systematic Review for a 2015 Update

Aims: Familial hypercholesterolemia (FH) is an autosomal dominant disorder with increased cardiovascular risk, caused by mutations in LDLR, APOB and PCSK 9 genes. Although it is described that over 1700 variants have been found, none of the existing databases are completely updated. The aim of this work is to construct a FH database in order to provide a unique source of verified information about variants associated with FH for a more accurate genetic diagnosis.

Network Analyis Approach to Find New Candidate Genes and Pathways Involved in the Pathophysiology of Familial Hypercholesterolemia

Introduction: Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD) due to lifelong elevated plasma low-density lipoprotein (LDL) levels. Worldwide only 40 % of patients (FH+) with a clinical diagnosis of FH carry a mutation in any of the three genes (namely: LDLR, APOB, PCSK 9) that are currently known to be associated to the disease. We guess that the remaining 60 % of the patients (FH-) probably includes a high percentage of individuals with a polygenic form of dyslipidemia or an environmental form of hypercholesterolemia and a small percentage of individuals with mutations in some novel genes, never associated before with dyslipidemias. Here we present the preliminary results of an integrative approach intended to identify new candidate genes and to dissect pathways that can be dysregulated in the disease.

Genetic Analysis of Familial Hypercholesterolemia in Iberoamerican Countries

The Iberoamerican Familial Hypercholesterolemia network (IBAFH_N) was created in 2013 to promote awareness for Familial Hypercholesterolemia (FH) in these countries – Argentina, Brazil, Chile, Mexico, Portugal, Spain, Uruguay and more recently Colombia – that share a past and history. The aim of this work was to perform a molecular analysis of FH mutations in Iberoamerica.

Using percentiles to diagnose familial hypercholesterolemia in Portugal

Aims: Familial hypercholesterolemia (FH) is a genetic disorder of lipid metabolism, clinically characterised by high levels of low-density lipoprotein cholesterol (LDL-C) that leads to cholesterol accumulation in tendons and arteries, premature atherosclerosis and increased risk of premature coronary heart disease. In 1999, the Portuguese FH Study was established at the National Institute of Health to identify the genetic cause of hypercholesterolemia in individuals with a clinical diagnosis of FH and to perform an epidemiologic study to determine the prevalence and distribution of FH in Portugal. In the last 16 years, a genetic defect was identified in 749 patients, representing 3. 7 % of the cases estimated to exist in Portugal. Index patients were included in this study using the Simon Broome (SB) criteria. However, there are different FH clinical criteria to diagnose index cases. Since there are no clinical criteria to identify relatives with FH, the aim of this work was to investigate if a diagnostic tool based on population specific 95 th percentile improves the clinical identification of Portuguese FH patients comparing with SB criteria.

e_LIPID: Characterisation of the Lipid Profile in the Portuguese Population

AIM: Cardiovascular disease (CVD), particularly coronary heart disease and stroke, are the leading cause of morbidity and mortality worldwide. The common forms of CVD have a complex etiology in which interactions between multiple genetic and environmental factors play an important role. Dyslipidaemia is one of many independent cardiovascular risk factors that have been identified for CVD, and its correct identification is of great importance in order to implement specific interventions, especially for CVD prevention. The aim of this study was the construction of population specific lipid percentiles and the to present the characterization of the dyslipidaemia in the Portuguese population.

Diminuição da expressão dos genes APP e CP em doentes de Alzheimer sugere alteração da exportação de ferro celular nesta demência

Recentemente tem-se assistido a um acumular de evidência sugerindo a implicação de uma desregulação do metabolismo do ferro (Fe) na fisiopatologia da doença de Alzheimer (DA). Neste trabalho, pretendemos esclarecer melhor os mecanismos moleculares subjacentes à homeostasia deste metal na DA, particularmente ao nível do efluxo celular. Assim, mediu-se em células mononucleares do sangue periférico de 73 doentes com DA e 74 controlos a expressão de genes diretamente envolvidos na regulação e exportação celular de Fe, utilizando a técnica de PCR quantitativo. Os resultados mostraram uma diminuição significativa na expressão dos genes aconitase (ACO1; P=0,007); ceruloplasmina (CP; P<0,001) e proteína precursora de beta amilóide (APP; P=0,006) em doentes com DA comparativamente com os voluntários saudáveis. Estas observações apontam para uma diminuição significativa da expressão dos genes associados com a exportação de Fe celular mediada pela ferroportina na DA. Assim, o presente estudo reforça resultados anteriores que mostram alterações no metabolismo do Fe e podem estar na origem da retenção intracelular deste metal e aumento de stress oxidativo caraterísticos desta patologia.

Vacinação antigripal da população portuguesa na época 2015/2016: estudo na amostra ECOS

Dando continuidade à monitorização da cobertura da vacina antigripal sazonal (VAGS), o Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA), através do Departamento de Epidemiologia, estudou a taxa de cobertura da VAGS na época 2015/2016. Este estudo teve como objetivos estimar a taxa de cobertura da vacina antigripal da população portuguesa residente no continente na época gripal de 2015/2016, nos grupos de risco, e por NUTS II, bem como caracterizar a prática da VAGS. O estudo epidemiológico, transversal, consistiu num inquérito realizado por entrevista telefónica e por via web à amostra de famílias ECOS (Em Casa Observamos Saúde), realizado entre março e maio de 2016 (1005 Unidades de Alojamento). A cobertura bruta da população pela VAGS foi 16,2% (IC95%: 13,5% a 19,5%) e 50,1% (IC95%: 42,1% a 58,1%) na população com 65 ou mais anos de idade. Comparativamente à época anterior, 2014/2015, os valores obtidos verificam-se semelhantes (17,1% na população geral e 50,9% na população com 65 ou mais anos). A vacinação antigripal sazonal decorreu, principalmente, nos Centros de Saúde do Serviço Nacional de Saúde (60,4%) seguido pela farmácia (30,6%). A amostra ECOS tem vindo a revelar-se, ao longo dos últimos anos, uma forma adequada de monitorização da cobertura da VAGS na população portuguesa, capaz de detetar alterações nas tendências de vacinação relacionadas com a implementação de medidas de Saúde Pública, entre as quais a gratuitidade da vacina para os idosos.

Network analysis approach to find new candidate genes and pathways involved in the pathophysiology of familial hypercholesterolemia

Still a big gap exists between clinical and genetic diagnosis of dyslipidemic disorders. Almost the 60% of the patients with a clinical diagnosis of Familial hypercholesterolemia (FH) still lack of a genetic diagnosis. Here we present the preliminary results of an integrative approach intended to identify new candidate genes and to dissect pathways that can be dysregulated in the disease. Interesting hits will be subsequently knocked down in vitro in order to evaluate their functional role in the uptake of fluorescently-labeled LDL and free cell cholesterol using automated microscopy.

Characterisation of the Lipid Profile of the Portuguese Population

Cardiovascular disease (CVD), particularly coronary heart disease (CHD) and stroke, are the leading cause of morbidity and mortality worldwide. The common forms of CVD have a complex aetiology in which interactions between multiple genetic and environmental factors play an important roles. The incidence rates of these diseases are increasing in developing countries as a result of the modification of lifestyles and increased prevalence of cardiovascular risk factors. Many independent cardiovascular risk factors could be modifiable, in contrast to the genetic risk factors. However, the associated risk of the genetic factors can be prevented if early identified, making genetic studies a priority in cardiovascular genetics research.

Identification of novel biomarkers to distinguish polygenic and monogenic dyslipidemia system biology approach

Dyslipidaemia is one of the major cardiovascular risk factors, it can be due to primary causes (i.e. monogenic, characterized by a single gene mutation, or dyslipidaemia of polygenic/environmental causes), or secondary to specific disorders such as obesity, diabetes mellitus or hypothyroidism. Monogenic patients present the most severe phenotype and so they need to be identified in early age so pharmacologic treatment can be implemented to decrease the cardiovascular risk. However the majority of hyperlipidemic patients most likely have a polygenic disease that can be mainly controlled just by the implementation of a healthy lifestyle. Thus, the distinction between monogenic and polygenic dyslipidaemia is important for a prompt diagnosis, cardiovascular risk assessment, counselling and treatment. Besides the already stated biomarkers as LDL, apoB and apoB/apoA-I ratio, other promising (yet, needing further research) biomarkers for clinical differentiation between dyslipidaemias are apoE, sdLDL, apoC-2 and apoC-3. However, none of these biomarkers can explain the complex lipid profile of the majority of these patients.

Functional genomics of Familial Hypercholesterolemia

Main Aim of the study: to identify the cause of the dyslipidaemia in patients with a clinical phenotype of Familial Hypercholesterolaemia (FH).