The island of Gran Canaria: A genetic isolate for familial hypercholesterolemia.

Background: Genetic diagnosis of familial hypercholesterolemia (FH) has not been universally performed in the Canary Islands (Spain).

Objectives: This study aimed to genetically characterize a cohort of patients with FH in the island of Gran Canaria.

Methods: Study subjects were 70 unrelated index cases attending a tertiary hospital in Gran Canaria, with a clinical diagnosis of FH, according to the criteria of the Dutch Lipid Clinic Network.

Evaluation of Chitotriosidase and CC-Chemokine Ligand 18 as Biomarkers of Microglia Activation in Amyotrophic Lateral Sclerosis.

Background: The development of biomarkers for use in diagnosing, monitoring disease progression and analyzing therapeutic trials response in amyotrophic lateral sclerosis (ALS) is essential.

Objective: The aim of this study was to identify inflammatory factors in plasma or cerebrospinal fluid (CSF) from patients with ALS with particular attention to specific markers of microglia activation as chitotriosidase (ChT) and chemokine (C-C motif) ligand 18 (CCL18) to determine its potential as ALS biomarkers.

Methods: We studied CSF and plasma samples from 32 patients and 42 healthy controls.

Sleep duration and subclinical atherosclerosis: The Aragon Workers' Health Study.

Background And Aims: Few studies have evaluated the association of sleep duration with subclinical atherosclerosis, and with heterogeneous findings. We evaluated the association of sleep duration with the presence of coronary, carotid, and femoral subclinical atherosclerosis in healthy middle-age men with low prevalence of clinical comorbidities.

Methods: We performed a cross-sectional analysis of 1968 men, 40-60 years of age, participating in the Aragon Workers' Health Study (AWHS).

Recommendations for the detection and diagnosis of Niemann-Pick disease type C: An update.

Purpose Of Review: Niemann-Pick disease type C (NP-C) is a neurovisceral disorder that may be more prevalent than earlier estimates. Diagnosis of NP-C is often delayed; a key aim for clinical practice is to reduce this delay. Recently, substantial progress has been made in the field of NP-C screening and diagnosis, justifying an update to the existing recommendations for clinical practice.

Autosomal Recessive Hypercholesterolemia: Long-Term Cardiovascular Outcomes.

Background: Autosomal recessive hypercholesterolemia (ARH) is a rare lipid disorder characterized by premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data for clinical management and cardiovascular outcomes in ARH.

Objectives: Evaluation of changes in lipid management, achievement of low-density lipoprotein cholesterol (LDL-C) goals and cardiovascular outcomes in ARH.

Autosomal recessive hypercholesterolemia in Spain.

Background And Aims: Autosomal recessive hypercholesterolemia (ARH) is a very rare disease, caused by mutations in LDL protein receptor adaptor 1 (LDLRAP1). It is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of premature cardiovascular disease. We aimed to characterize ARH in Spain.

ABCG5/G8 gene is associated with hypercholesterolemias without mutation in candidate genes and noncholesterol sterols.

Context: Approximately 20% to 40% of clinically defined familial hypercholesterolemia (FH) cases do not show a causative mutation in candidate genes (mutation-negative FH), and some of them may have a polygenic origin.

Objective: The aim of this work was to study the prevalence of ABCG5/G8 genetic variants in mutation-negative FH, as defects in these genes relate to intestinal hyperabsorption of cholesterol and thus ABCG5/G8 variants could explain in part the mechanism of hypercholesterolemia.

Design, Setting, And Patients: We sequenced the ABCG5/G8 genes in 214 mutation-negative FH and 97 controls.

Functional analysis of new 3' untranslated regions genetic variants in genes associated with genetic hypercholesterolemias.

Background: Familial hypercholesterolemia (FH) is the best-described autosomal dominant genetic hypercholesterolemia (GH). Mutations in candidate genes can explain a high proportion of FH cases, but for many, no causative mutations are detected (designed non-FG-GH), suggesting the existence of additional genetic variants associated with the disease.

Objective: We aimed to identify new single-nucleotide variants (SNVs) located at the 3' untranslated regions (3'UTRs) of the low-density lipoprotein receptor, low-density lipoprotein receptor-related protein-associated protein 1, ATP-binding cassette sub-family G member 5, and sterol regulatory element-binding protein 2 genes in non-FH-GH individuals and investigated whether the association of these SNVs with non-FH-GH could be explained by changes in the affinity of regulatory microRNAs (miRNA) targeting the sequences modified by the SNVs.

The hidden Niemann-Pick type C patient: clinical niches for a rare inherited metabolic disease.

Background: Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields.

Twelve years of experience with miglustat in the treatment of type 1 Gaucher disease: The Spanish ZAGAL project.

We report data from a prospective, observational study (ZAGAL) evaluating miglustat 100mg three times daily orally. in treatment-naïve patients and patients with type 1 Gaucher Disease (GD1) switched from previous enzyme replacement therapy (ERT). Clinical evolution, changes in organ size, blood counts, disease biomarkers, bone marrow infiltration (S-MRI), bone mineral density by broadband ultrasound densitometry (BMD), safety and tolerability annual reports were analysed.

Homozygous Familial Hypercholesterolemia in Spain: Prevalence and Phenotype-Genotype Relationship.

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDL protein receptor adaptor 1 (LDLRAP1). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition.

Rare genetic variants with large effect on triglycerides in subjects with a clinical diagnosis of familial vs nonfamilial hypertriglyceridemia.

Background: Most primary severe hypertriglyceridemias (HTGs) are diagnosed in adults, but their molecular foundations have not been completely elucidated.

Objective: We aimed to identify rare dysfunctional mutations in genes encoding regulators of lipoprotein lipase (LPL) function in patients with familial and non-familial primary HTG.

Methods: We sequenced promoters, exons, and exon-intron boundaries of LPL, APOA5, LMF1, and GPIHBP1 in 118 patients with severe primary HTG (triglycerides >500 mg/dL) and 53 normolipidemic controls.

Genetic Variants of LDLR and PCSK9 Associated with Variations in Response to Antihypercholesterolemic Effects of Armolipid Plus with Berberine.

Background: Armolipid Plus (AP) is a nutraceutical that contains policosanol, fermented rice with red yeast, berberine, coenzyme Q10, folic acid, and astaxanthin. It has been shown to be effective in reducing plasma LDL cholesterol (LDLc) levels. In the multicenter randomized trial NCT01562080, there was large interindividual variability in the plasma LDLc response to AP supplementation.

Femoral and Carotid Subclinical Atherosclerosis Association With Risk Factors and Coronary Calcium: The AWHS Study.

Background: Early subclinical atherosclerosis has been mainly researched in carotid arteries. The potential value of femoral arteries for improving the predictive capacity of traditional risk factors is an understudied area.

Objectives: This study sought to evaluate the association of subclinical carotid and femoral plaques with risk factors and coronary artery calcium score (CACS) in middle-aged men.

Increased glycolipid storage produced by the inheritance of a complex intronic haplotype in the α-galactosidase A (GLA) gene.

Background: Accumulation of galactosphingolipids is a general characteristic of Fabry disease, a lysosomal storage disorder caused by the deficient activity of α-galactosidase A encoded by the GLA gene. Although many polymorphic GLA haplotypes have been described, it is still unclear whether some of these variants are causative of disease symptoms. We report the study of an inheritance of a complex intronic haplotype (CIH) (c.

Glycated Hemoglobin, Fasting Insulin and the Metabolic Syndrome in Males. Cross-Sectional Analyses of the Aragon Workers' Health Study Baseline.

Background And Aims: Glycated hemoglobin (HbA1c) is currently used to diagnose diabetes mellitus, while insulin has been relegated to research. Both, however, may help understanding the metabolic syndrome and profiling patients. We examined the association of HbA1c and fasting insulin with clustering of metabolic syndrome criteria and insulin resistance as two essential characteristics of the metabolic syndrome.

The influence of genetic variability and proinflammatory status on the development of bone disease in patients with Gaucher disease.

Gaucher disease, the most common lysosomal storage disorder, is caused by β-glucocerebrosidase deficiency. Bone complications are the major cause of morbidity in patients with type 1 Gaucher disease (GD1). Genetic components strongly influence bone remodelling.

[Identification of variants in LMF1 gene associated with primary hypertriglyceridemia].

The majority of severe primary hypertriglyceridemia (HTG) are diagnosed in adults, and their molecular bases have not yet been fully defined. The promoter, coding regions and intron-exon boundaries of LMF1 were sequenced in 112 patients with severe primary hipertrigliceridemia (defined as TG above 500mg/dl). Five patients (4.

Association of ferritin elevation and metabolic syndrome in males. Results from the Aragon Workers' Health Study (AWHS).

Context: Ferritin concentration is associated with metabolic syndrome, but the possibility of a nonlinear association has never been explored.

Objective: This study aimed to examine the relationship between serum ferritin levels and the metabolic syndrome in Spanish adult males.

Design: This was a cross-sectional analysis of baseline data from the Aragon Workers' Health Study.

Common genetic variants contribute to primary hypertriglyceridemia without differences between familial combined hyperlipidemia and isolated hypertriglyceridemia.

Background: The majority of hypertriglyceridemias are diagnosed as familial combined hyperlipidemia (FCHL) and primary isolated hypertriglyceridemias. The contribution of common genetic variants in primary hypertriglyceridemias and the genetic difference between FCHL and isolated hypertriglyceridemias have not been thoroughly examined.

Methods And Results: This study involved 580 patients with hypertriglyceridemias and 403 controls.

A genetic variant in the LDLR promoter is responsible for part of the LDL-cholesterol variability in primary hypercholesterolemia.

Background: GWAS have consistently revealed that LDLR locus variability influences LDL-cholesterol in general population. Severe LDLR mutations are responsible for familial hypercholesterolemia (FH). However, most primary hypercholesterolemias are polygenic diseases.