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.

Consequences of twenty-first-century policy for multi-millennial climate and sea-level change

Most of the policy debate surrounding the actions needed to mitigate and adapt to anthropogenic climate change has been framed by observations of the past 150 years as well as climate and sea-level projections for the twenty-first century. The focus on this 250-year window, however, obscures some of the most profound problems associated with climate change. Here, we argue that the twentieth and twenty-first centuries, a period during which the overwhelming majority of human-caused carbon emissions are likely to occur, need to be placed into a long-term context that includes the past 20 millennia, when the last Ice Age ended and human civilization developed, and the next ten millennia, over which time the projected impacts of anthropogenic climate change will grow and persist. This long-term perspective illustrates that policy decisions made in the next few years to decades will have profound impacts on global climate, ecosystems and human societies — not just for this century, but for the next ten millennia and beyond.