Clin Investig Arterioscler 2018 Mar 27. Epub 2018 Mar 27.

Unitat de Medicina Vascular i Metabolisme, Hospital Universitari Sant Joan, Unitat d'Investigació en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, Institut d'Investigació Sanitària Pere Virgili (IISPV), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas (CIBERDEM), Reus, Tarragona, España.

Background: Familial hypercholesterolaemia (FH) in children is under-detected and is difficult to diagnose in clinical practice. The aim of this study was to evaluate clinical, biochemical and vascular imaging variables in order to detect children and adolescents with FH.

Methods: A total of 222 children aged 4-18 years old were recruited to participate in a project for the early detection of FH (The DECOPIN Project). Read More

Vnitr Lek 2018 ;64(1):25-29

Familial combined hyperlipidemia (FCH) is the most frequent genetic dyslipidemia (DLP) with high risk of early atherosclerosis manifestation. It is characterized by elevated both triglycerides 1.5 mmol/l and apolipoprotein B 1. Read More

Circulation 2018 Feb;137(8):820-831

Department of Pediatrics, Section Molecular Genetics, University Medical Center Groningen, University of Groningen, the Netherlands (J.-W.B., A.R., P.L., J.A.K.)

Background: Atherosclerosis starts in childhood but low-density lipoprotein cholesterol (LDL-C), a causal risk factor, is mostly studied and dealt with when clinical events have occurred. Women are usually affected later in life than men and are underdiagnosed, undertreated, and understudied in cardiovascular trials and research. This study aims at a better understanding of lifestyle and genetic factors that affect LDL-C in young women. Read More

Atherosclerosis 2018 Mar 31;270:117-122. Epub 2018 Jan 31.

Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Universitat Rovira i Virgili, IISPV, Reus, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.

Background And Aims: Familial hypercholesterolaemia (FH) is underdiagnosed in children. In addition to lipid concentrations, lipoprotein particle quantity and quality could influence cardiovascular risk. We aimed to perform a comprehensive plasma lipid study, including lipoprotein particle number and size assessment by two-dimensional nuclear magnetic resonance (2D-1H-NMR), in children with FH compared to non-affected children and to evaluate the clinical value of these factors as subclinical atherosclerosis biomarkers. Read More

Curr Opin Lipidol 2018 Apr;29(2):65-71

Purpose Of Review: We provide an overview of molecular diagnosis for familial hypercholesterolemia in France including descriptions of the mutational spectrum, polygenic susceptibility and perspectives for improvement in familial hypercholesterolemia diagnosis.

Recent Findings: Molecular testing for familial hypercholesterolemia is recommended for patients with a LDL-cholesterol level above 190 mg/dl (adults) associated with criteria related to personal and family history of hypercholesterolemia and premature cardiovascular disease. Among the 3381 index cases included with these characteristics in the French registry for familial hypercholesterolemia, 2054 underwent molecular diagnosis and 1150 (56%) were found to have mutations (93. Read More

Eur J Hum Genet 2018 Apr 26;26(4):570-578. Epub 2018 Jan 26.

LVTS, INSERM U1148, Paris, France.

Familial hypercholesterolemia (FH) is caused by mutations in LDLR (low-density lipoprotein receptor), APOB (apolipoprotein B), PCSK9 (proprotein convertase subtilisin/kexin type 9), or APOE (apolipoprotein E) genes in approximately 80% of the cases. Polygenic forms of hypercholesterolemia may be present among patients clinically diagnosed with FH but with no identified mutation (FH mutation-negative (FH/M-)). To address whether polygenic forms may explain phenocopies in FH families, we calculated a 6-single-nucleotide polymorphism (SNP) genetic risk score (GRS) in all members from five French FH families where a mutation was identified (FH/M+) as well as some phenocopies (FH/M-). Read More

J Nutr Biochem 2018 Mar 27;53:48-57. Epub 2017 Nov 27.

Instituto de Investigación Sanitaria Aragón (IIS Aragón), Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Universidad de Zaragoza, CIBERCV, Zaragoza, Spain.

Primary hypercholesterolemia of genetic origin, negative for mutations in LDLR, APOB, PCSK9 and APOE genes (non-FH GH), and familial combined hyperlipidemia (FCHL) are polygenic genetic diseases that occur with hypercholesterolemia, and both share a very high cardiovascular risk. In order to better characterize the metabolic abnormalities associated with these primary hypercholesterolemias, we used noncholesterol sterols, as markers of cholesterol metabolism, to determine their potential differences. Hepatic cholesterol synthesis markers (desmosterol and lanosterol) and intestinal cholesterol absorption markers (sitosterol and campesterol) were determined in non-FH GH (n=200), FCHL (n=100) and genetically defined heterozygous familial hypercholesterolemia subjects (FH) (n=100) and in normolipidemic controls (n=100). Read More

Proteomics Clin Appl 2018 Jan 11;12(1). Epub 2017 Dec 11.

Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at the Heinrich-Heine-University Duesseldorf, Leibniz Center for Diabetes Research, Duesseldorf, Germany.

Purpose: Metabolic syndrome (MetS) consists of five risk factors: elevated blood pressure and fasting glucose, visceral obesity, dyslipidemia, and hypercholesterinemia. The physiological impact of lipid metabolism indicated as visceral obesity and hepatic lipid accumulation on MetS is still under debate. One major cause of disturbed lipid metabolism might be dysfunction of cellular organelles controlling energy homeostasis, i. Read More

J Clin Lipidol 2017 Nov - Dec;11(6):1432-1440.e4. Epub 2017 Oct 4.

Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBERCV, Universidad de Zaragoza, Zaragoza, Spain.

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. Read More

J Am Coll Cardiol 2017 Oct;70(14):1732-1740

Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain; CIBER in Cardiovascular Diseases (CIBERCV), Madrid, Spain; Faculty of Health Sciences, University Francisco de Vitoria (UFV), Pozuelo de Alarcon, Madrid, Spain. Electronic address:

Background: Genetic screening programs in unselected individuals with increased levels of low-density lipoprotein cholesterol (LDL-C) have shown modest results in identifying individuals with familial hypercholesterolemia (FH).

Objectives: This study assessed the prevalence of genetically confirmed FH in patients with acute coronary syndrome (ACS) and compared the diagnostic performance of FH clinical criteria versus FH genetic testing.

Methods: Genetic study of 7 genes (LDLR, APOB, PCSK9, APOE, STAP1, LDLRAP1, and LIPA) associated with FH and 12 common alleles associated with polygenic hypercholesterolemia was performed in 103 patients with ACS, age ≤65 years, and LDL-C levels ≥160 mg/dl. Read More

Rev Esp Cardiol (Engl Ed) 2017 Sep 14. Epub 2017 Sep 14.

Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBERCV, Universidad de Zaragoza, Zaragoza, Spain.

Introduction And Objectives: Approximately 20% to 40% of clinically defined familial hypercholesterolemia cases do not show a causative mutation in candidate genes, and some of them may have a polygenic origin. A cholesterol gene risk score for the diagnosis of polygenic hypercholesterolemia has been demonstrated to be valuable to differentiate polygenic and monogenic hypercholesterolemia. The aim of this study was to determine the contribution to low-density lipoprotein cholesterol (LDL-C) of the single nucleotide variants associated with polygenic hypercholesterolemia in probands with genetic hypercholesterolemia without mutations in candidate genes (nonfamilial hypercholesterolemia genetic hypercholesterolemia) and the genetic score in cascade screening in their family members. Read More

Adv Ther 2017 Aug 7;34(8):1966-1975. Epub 2017 Jul 7.

Department of Medicine and Surgery Sciences, University of Bologna, Bologna, Italy.

Introduction: There is a growing interest in nutraceuticals improving cardiovascular risk factor levels and related organ damage.

Methods: This double-blind, placebo-controlled randomized clinical trial aims to compare the effect of a combined nutraceutical containing red yeast rice (10 mg), phytosterols (800 mg), and L-tyrosol (5 mg) on lipid profile, blood pressure, endothelial function, and arterial stiffness in a group of 60 patients with polygenic hypercholesterolemia resistant to Mediterranean diet.

Results: After 8 weeks of treatment, when compared to the placebo group, the active treated patients experienced a more favorable percentage change in total cholesterol (-16. Read More

J Physiol Anthropol 2017 Jun 14;36(1):25. Epub 2017 Jun 14.

Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman (UTAR) Kampar Campus, Jalan Universiti, Bandar Barat, 31900, Kampar, Perak, Malaysia.

Background: Despite the fact that insertions/deletions (INDELs) are the second most common type of genetic variations and variable number tandem repeats (VNTRs) represent a large portion of the human genome, they have received far less attention than single nucleotide polymorphisms (SNPs) and larger forms of structural variation like copy number variations (CNVs), especially in genome-wide association studies (GWAS) of complex diseases like polygenic obesity. This is exemplified by the vast amount of review papers on the role of SNPs and CNVs in obesity, its related traits (like anthropometric measurements, biochemical variables, and eating behavior), and its related complications (like hypertension, hypertriglyceridemia, hypercholesterolemia, and insulin resistance-collectively known as metabolic syndrome). Hence, this paper reviews the types of INDELs and VNTRs that have been studied for association with obesity and its related traits and complications. Read More

Lipids Health Dis 2017 Jun 2;16(1):103. Epub 2017 Jun 2.

Human Genetics Unit, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo, 00800, Sri Lanka.

Hypercholesterolemia is a strong determinant of mortality and morbidity associated with cardiovascular diseases and a major contributor to the global disease burden. Mutations in four genes (LDLR, APOB, PCSK9 and LDLRAP1) account for the majority of cases with familial hypercholesterolemia. However, a substantial proportion of adults with hypercholesterolemia do not have a mutation in any of these four genes. Read More

Ann Cardiol Angeiol (Paris) 2018 Feb 31;67(1):1-8. Epub 2017 May 31.

Hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France. Electronic address:

Background: Familial hypercholesterolemia is a monogenic autosomal dominant dyslipidemia characterized by a permanent and isolated increase of cholesterol carried by low-density lipoproteins. The prevalence of its heterozygous form is estimated between 1/500 and 1/250, and in the absence of specific treatment, this form is responsible for an increase by a factor of 13 of the risk of premature coronary artery disease compared to patients non-affected by the disease.

Objectives: To perform an inventory of the knowledge of heterozygous familial hypercholesterolemia in France for physicians involved in the management of the disease. Read More

Atherosclerosis 2017 Aug 13;263:405-411. Epub 2017 May 13.

Centre for Cardiovascular Genetics, University College London, The Rayne Institute, University Street, London, WC1E 6JF, UK. Electronic address:

Background And Aims: Familial hypercholesterolemia (FH) is a common inherited disorder of low density lipoprotein-cholesterol (LDL-C) metabolism. It is associated with higher risk of premature coronary heart disease. Around 60% of patients with a clinical diagnosis of FH do not have a detectable mutation in the genes causing FH and are most likely to have a polygenic cause for their raised LDL-C. Read More

Herz 2017 Aug;42(5):440-448

Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität München, Lazarettstr. 36, 80636, München, Deutschland.

Genetic testing plays an increasing role in cardiovascular medicine. Advances in technology and the development of novel and more affordable (high throughput) methods have led to the identification of genetic risk factors in research and clinical practice. Also, this progress has simplified the screening of patients and individuals at risk. Read More

J Clin Lipidol 2017 Jul - Aug;11(4):880-890. Epub 2017 May 19.

NYU School of Medicine & NYU Center for Prevention of Cardiovascular Disease, New York, NY, USA.

An Expert Panel convened by the National Lipid Association was charged with updating the recommendations on the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody therapy that were provided by the 2015 National Lipid Association Recommendations for the Patient-Centered Management of Dyslipidemia: Part 2. Recent studies have demonstrated the efficacy of these agents in reducing low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol and have confirmed their excellent safety profile. A cardiovascular outcomes study has shown that these agents reduce incident atherosclerotic cardiovascular disease (ASCVD) events in patents with stable ASCVD and concomitant risk factors. Read More

Expert Rev Mol Diagn 2017 Jul 29;17(7):641-651. Epub 2017 May 29.

a Departments of Medicine and Biochemistry, Schulich School of Medicine and Dentistry , Western University , London , Canada.

Introduction: Familial hypercholesterolemia (FH) is a common genetic cause of premature coronary heart disease that is widely underdiagnosed and undertreated. To improve the identification of FH and initiate timely and appropriate treatment strategies, genetic testing is becoming increasingly offered worldwide as a central part of diagnosis. Areas covered: Recent advances have been propelled by an improved understanding of the genetic determinants of FH together with substantially reduced costs of appropriate screening strategies. Read More

Curr Opin Lipidol 2017 Aug;28(4):313-320

aMolecular Diagnostics, Randox Laboratories Ltd., Crumlin bRegional Genetics Centre, Belfast City Hospital, Belfast Health and Social Care Trust, Belfast, UK.

Purpose Of Review: Familial hypercholesterolaemia is a hereditary disorder of lipoprotein metabolism which causes a lifelong increase in LDL-C levels resulting in premature coronary heart disease. The present review looks at some of the recent literature on how molecular methods can be used to assist in the definitive diagnosis of familial hypercholesterolaemia in a range of patient groups.

Recent Findings: Several recent studies have shown that the prevalence of clinical familial hypercholesterolaemia is higher than previously thought at 1/200 to 1/300, and that 2-5% of patients presenting with early myocardial infarction can be found to have a familial hypercholesterolaemia mutation. Read More

J Clin Lipidol 2017 May - Jun;11(3):725-732.e5. Epub 2017 Apr 6.

Nutrition, Metabolism and Atherosclerosis Clinic, Institut de recherches cliniques de Montréal, Québec, Canada; Division of Experimental Medicine, Department of Medicine, McGill University, Québec, Canada; Division of Medical Biochemistry, Department of Medicine, McGill University, Québec, Canada. Electronic address:

Background: Although familial hypercholesterolemia (FH) is a severe monogenic disease, it has been shown that clinical risk factors and common genetic variants can modify cardiovascular disease (CVD) risk.

Objective: The aim of the study was to evaluate the polygenic contribution to lipid traits and CVD in FH using genetic risk scores (GRSs).

Methods: Among the 20,434 subjects attending the lipid clinic, we identified and included 725 individuals who carried an FH causing mutation in this retrospective cohort study. Read More

Curr Cardiol Rep 2017 May;19(5):44

Institute of Cardiovascular Science, University College London, 5 University St, London, WC1E 6JF, UK.

Purpose Of Review: Familial hypercholesterolaemia (FH) is an inherited disorder of low-density lipoprotein cholesterol (LDL-C) which is characterised by a raised cholesterol level from birth and a high risk of premature coronary heart disease. In this paper, we review the genetic basis of FH and its impact on the clinical presentation.

Recent Findings: Mutations in any of three genes (LDLR, APOB and PCSK9) are known to cause autosomal dominant FH, but a mutation can be found in only ∼40% of patients with a clinical diagnosis of FH. Read More

Physiol Res 2017 Apr;66(Supplementum 1):S101-S111

Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Since 2007, the year of their first widespread use, genome-wide association studies (GWAS) have become the "gold standard" for the detection of causal genes and polymorphisms in all fields of human medicine. Cardiovascular disease (CVD), one of the major causes of morbidity and mortality, is no exception. The first GWAS focused on hypercholesterolemia and dyslipidemia as the major CVD determinants. Read More

Rev Esp Cardiol (Engl Ed) 2017 Jul 17;70(7):551-558. Epub 2017 Feb 17.

Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.

Introduction And Objectives: The equations used in the general population to calculate cardiovascular risk are not useful in genetic hypercholesterolemia (GH). Carotid plaque detection has proved useful in cardiovascular prediction and risk reclassification but there have been no studies of its usefulness in GH. The aim of this study was to determine the association between the presence of carotid artery plaque and the occurrence of cardiovascular events in patients with GH. Read More

Cardiovasc Pathol 2017 Mar - Apr;27:71-75. Epub 2017 Jan 29.

Department of Cardiovascular Sciences and the NIHR Leicester Cardiovascular Biomedical Research Unit, University of Leicester, Leicester, UK.

Atherosclerosis and abdominal aortic aneurysms (AAAs) are multifactorial and polygenic diseases with known environmental and genetic risk factors that contribute toward disease development. Atherosclerosis represents an important independent risk factor for AAA, as people with AAA often have atherosclerosis. Studies have shown that comorbidity is usually between ~25% and 55%, but it is still not fully known whether this association is causal or a result of common shared risk profiles. Read More

J Pediatr 2017 Apr 1;183:100-107.e3. Epub 2017 Feb 1.

Department of Internal Medicine and Allied Sciences, Sapienza University of Rome, Rome, Italy. Electronic address:

Objective: To evaluate the effectiveness of criteria based on child-parent assessment in predicting familial hypercholesterolemia (FH)-causative mutations in unselected children with hypercholesterolemia.

Study Design: LDLR, APOB, and PCSK9 genes were sequenced in 78 children and adolescents (mean age 8.4 ± 3. Read More

Vnitr Lek Fall 2016;62(11):882-886

Hyperlipoproteinemia (HLP) is one of the most common metabolic disorder in childhood. We assume that 20 % of children have a disorder of the lipid metabolism. Some HLP are very common in the population, and moderate, and some are very rare, but are very severe. Read More

Atherosclerosis 2017 Feb 18;257:55-63. Epub 2016 Dec 18.

Center for Research Prevention and Treatment of Atherosclerosis, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel.

Background And Aims: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the genes for LDL receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type9 (PCSK9). The purpose of the current investigation was to define the current spectrum of mutations causing FH in Israel.

Methods: New families were collected through the MEDPED (Make Early Diagnosis Prevent Early Death) FH program. Read More

JIMD Rep 2017 9;35:67-70. Epub 2016 Dec 9.

Robarts Research Institute and Department of Medicine, Schulich School of Medicine, Western University, London, ON, Canada, N6A 5B7.

Familial hypercholesterolemia (FH) is an autosomal codominantly inherited disease. The severity of clinical presentation depends on the zygosity of the mutations in the LDLR, APOB, or PCSK9 genes. The homozygous form (HoFH) is associated with high mortality rate by third decade of life, while individuals with HeFH begin to suffer from premature cardiovascular disease in fourth or fifth decade of life. Read More

J Clin Lipidol 2016 Nov - Dec;10(6):1397-1405.e2. Epub 2016 Sep 22.

Departamento de Anatomía, Embriología y Genetica Animal, Universidad de Zaragoza, Zaragoza, Spain.

Background: A substantial proportion of individuals clinically diagnosed as familial hypercholesterolemia (FH) do not carry pathogenic mutations in candidate genes. Whether in them the high cholesterol trait is transmitted monogenically has not been studied.

Objectives: We assessed the inheritance pattern, penetrance, and expression of high low-density lipoprotein (LDL)-cholesterol (LDLc) in families with genetic hypercholesterolemia (GH) without known causative mutations (non-FH-GH). Read More

Arterioscler Thromb Vasc Biol 2016 Dec 20;36(12):2439-2445. Epub 2016 Oct 20.

From the Robarts Research Institute (J.W., J.S.D., M.R.B., J.F.R., A.D.M., A.A.D., H.C., M.W.H., R.A.H.), Department of Biochemistry (J.S.D., M.A., A.A.D., M.W.H., R.A.H.), and Department of Medicine (P.J.Z., M.W.H., R.A.H.), Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada; Faculté de Médicine, Université de Montréal, Québec, Canada (M.-P.D., G.L., J.-C.T.); and Montréal Heart institute, Québec, Canada (D.R., C.L.-K., M.-P.D., G.L., J.-C.T.).

Objective: Next-generation sequencing technology is transforming our understanding of heterozygous familial hypercholesterolemia, including revision of prevalence estimates and attribution of polygenic effects. Here, we examined the contributions of monogenic and polygenic factors in patients with severe hypercholesterolemia referred to a specialty clinic.

Approach And Results: We applied targeted next-generation sequencing with custom annotation, coupled with evaluation of large-scale copy number variation and polygenic scores for raised low-density lipoprotein cholesterol in a cohort of 313 individuals with severe hypercholesterolemia, defined as low-density lipoprotein cholesterol >5. Read More

Crit Rev Clin Lab Sci 2017 Jan 1;54(1):26-48. Epub 2016 Oct 1.

b Department of Cell Biology , State University of New York Downstate Medical Center , Brooklyn , NY , USA.

Homozygous familial hypercholesterolemia (HoFH) is a polygenic disease arising from defects in the clearance of plasma low-density lipoprotein (LDL), which results in extremely elevated plasma LDL cholesterol (LDL-C) and increased risk of atherosclerosis, coronary heart disease, and premature death. Conventional lipid-lowering therapies, such as statins and ezetimibe, are ineffective at lowering plasma cholesterol to safe levels in these patients. Other therapeutic options, such as LDL apheresis and liver transplantation, are inconvenient, costly, and not readily available. Read More

Med J Aust 2016 Sep;205(5):232-6

University of Western Australia, Perth, WA.

Familial hypercholesterolaemia (FH) is the most common autosomal dominant condition, with a prevalence of between one in 200 and one in 350 people in the general population. Untreated FH is associated with premature atherosclerotic cardiovascular disease (CVD). The prevalence of homozygous or compound heterozygous FH is now considered to be about one in 300 000 people. Read More

J Clin Lipidol 2016 Jul-Aug;10(4):851-859. Epub 2016 Mar 21.

Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Background: Familial hypercholesterolemia (FH) is caused by mutations in LDLR, APOB, or PCSK9, and in a previous study, we identified a causative mutation in these FH genes in 95% (255 of 269) of children with the FH phenotype. It has been hypothesized that a polygenic form of hypercholesterolemia is present in FH patients in whom no mutation is identified in the 3 FH genes.

Objective: To address whether a polygenic form of hypercholesterolemia, defined as high-weighted effect of low-density lipoprotein cholesterol (LDL-C) raising SNPs expressed as the genetic risk score (GRS), is present in the remaining 14 children. Read More

Heart 2016 07 28;102(13):1003-8. Epub 2016 Apr 28.

Department of Clinical Biochemistry, Royal Free Hospital, London, UK.

Familial hypercholesterolaemia (FH) is a common autosomal-dominant disorder in most European countries. Patients with FH are characterised by a raised level of low-density lipoprotein cholesterol and a high risk of premature coronary heart disease (CHD). Currently there is no consensus regarding the clinical utility to predict future coronary events or testing for the presence of subclinical atherosclerotic disease in asymptomatic patients with FH. Read More

Metabolism 2016 Mar 10;65(3):48-53. Epub 2015 Nov 10.

Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences, University College London, London, UK. Electronic address:

Background: Familial hypercholesterolemia (FH) is a common autosomal dominant disorder with a frequency of 1 in 200 to 500 in most European populations. Mutations in LDLR, APOB and PCSK9 genes are known to cause FH. In this study, we analyzed the genetic spectrum of the disease in the understudied Polish population. Read More

Atherosclerosis 2016 Dec 4;255. Epub 2016 Dec 4.

Department of Clinical Biochemistry, Royal Free London NHS Foundation Trust, London, UK; Cardiovascular Genetic Lab, University College London, UK.

Curr Genet Med Rep 2016 7;4(3):130-141. Epub 2016 Jun 7.

Departments of Medicine and Biochemistry, and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 4288A - 1151 Richmond Street North, London, ON N6A 5B7 Canada.

Purpose Of Review: Plasma lipids, namely cholesterol and triglyceride, and lipoproteins, such as low-density lipoprotein (LDL) and high-density lipoprotein, serve numerous physiological roles. Perturbed levels of these traits underlie monogenic dyslipidemias, a diverse group of multisystem disorders. We are on the verge of having a relatively complete picture of the human dyslipidemias and their components. Read More

BMC Genet 2015 Dec 23;16:148. Epub 2015 Dec 23.

Department of Mathematics and Statistics, Utah State University, 3900 Old Main, Logan, 84322, UT, USA.

Background: Genome-wide association studies (GWAS) interrogate large-scale whole genome to characterize the complex genetic architecture for biomedical traits. When the number of SNPs dramatically increases to half million but the sample size is still limited to thousands, the traditional p-value based statistical approaches suffer from unprecedented limitations. Feature screening has proved to be an effective and powerful approach to handle ultrahigh dimensional data statistically, yet it has not received much attention in GWAS. Read More

J Clin Lipidol 2015 Nov-Dec;9(6):751-757. Epub 2015 Aug 7.

Department of Emergency and Critical Care Medicine, School of Medicine, Keio University, Tokyo, Japan.

Background: Plasma-oxidized (ox) low-density lipoprotein (LDL) is an atherogenic lipoprotein. The distribution of ox-LDL in plasma LDL subfractions and the effect of statins on this distribution have not been investigated in detail.

Objective: We examined the distribution of cholesterol and ox-LDL in 3 ultracentrifugally separated plasma LDL subfractions and investigated the effects of a statin, rosuvastatin, on the levels of these lipoproteins. Read More

J Med Food 2015 Nov 14;18(11):1270-3. Epub 2015 Aug 14.

4 Internal Medicine and Medical Specialties Biomedical Department, University of Palermo , Palermo, Italy .

The main guidelines for cardiovascular disease prevention suggest that nutraceuticals could be an efficacious tool to improve lipid pattern. Our aim was to carry out a clinical trial comparing the metabolic effects of a combined nutraceutical containing both red yeast rice and polyunsaturated fatty acids (PUFAs) and a phytosterol-based approach in a setting of clinical practice. This was a multicenter open study with parallel control. Read More

Atherosclerosis 2015 Sep 30;242(1):8-12. Epub 2015 Jun 30.

Department of Oral Biology, College of Dentistry, Yonsei University, Seoul, South Korea. Electronic address:

Background/objective: Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by mutations in LDLR, APOB, or PCSK9. Polygenicity is a plausible cause in mutation-negative FH patients based on LDL cholesterol (LDL-C)-associated single nucleotide polymorphisms (SNPs) identified by the Global Lipids Genetics Consortium (GLGC). However, there are limited data regarding the polygenic cause of FH in Asians. Read More

J Clin Lipidol 2015 Mar-Apr;9(2):210-6. Epub 2014 Dec 16.

Department of Emergency Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.

Background: Plasma levels of low-density lipoproteins (LDLs) are decreased through stimulation of their hepatic uptake by statins via an LDL receptor. However, it is unclear whether statins equally stimulate the hepatic uptake of all LDL subfractions.

Objective: We compared the effects of atorvastatin on 3 LDL subfractions, and their associations with LDL-receptor activities, in Japanese patients with polygenic hypercholesterolemia (PHC), familial combined hyperlipoproteinemia (FCHL), and familial hypercholesterolemia (FH). Read More

Curr Opin Lipidol 2015 Jun;26(3):162-8

aPublic Health Department, Corporate Services, Hampshire County Council, Winchester, Hampshire bSolutions for Public Health, Oxford Business Park South, Cowley, Oxfordshire cCentre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.

Purpose Of Review: Many international recommendations for the management of familial hypercholesterolaemia propose the use of cascade testing using the family mutation to unambiguously identify affected relatives. In the current economic climate DNA information is often regarded as too expensive. Here, we review the literature and suggest strategies to improve cost-effectiveness of cascade testing. Read More

Clin Chem 2015 Jan 20;61(1):231-8. Epub 2014 Nov 20.

Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Institute of Cardiovascular Sciences, and

Background: Familial hypercholesterolemia (FH) is an autosomal-dominant disorder caused by mutations in 1 of 3 genes. In the 60% of patients who are mutation negative, we have recently shown that the clinical phenotype can be associated with an accumulation of common small-effect LDL cholesterol (LDL-C)-raising alleles by use of a 12-single nucleotide polymorphism (12-SNP) score. The aims of the study were to improve the selection of SNPs and replicate the results in additional samples. Read More

J Med Genet 2014 Aug 1;51(8):537-44. Epub 2014 Jul 1.

British Heart Foundation Laboratories, Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, the Rayne Building University College London, London, UK.

Background: Familial hypercholesterolaemia (FH) is an autosomal dominant disease of lipid metabolism, which leads to early coronary heart disease. Mutations in LDLR, APOB and PCSK9 can be detected in 80% of definite FH (DFH) patients. This study aimed to identify novel FH-causing genetic variants in patients with no detectable mutation. Read More

Curr Opin Lipidol 2014 Aug;25(4):274-81

Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.

Purpose Of Review: Genome-Wide Association Studies have provided robust identification of approximately 100 genetic loci determining plasma lipid parameters. Using these multiple common genetic lipid-determining variants in a 'gene score' has thrown new light on the mode of inheritance of familial lipid disorders.

Recent Findings: Different hypertriglyceridaemia states have been explained by the polygenic coinheritance of triglyceride-raising alleles. Read More

BMC Med Genomics 2014 Apr 7;7:17. Epub 2014 Apr 7.

Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, C, Pedro Cerbuna 12, 50009 Zaragoza, Spain.

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. Read More

Curr Opin Lipidol 2014 Jun;25(3):183-8

Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil.

Purpose Of Review: The purpose of this review is to describe advances in the diagnosis, cause, metabolism, risk factors for atherosclerosis, and treatment of familial hypercholesterolemia.

Recent Findings: Heterozygous familial hypercholesterolemia is almost four-fold more frequent than previously thought and is associated with 10-fold to 13-fold risk of cardiovascular disease comparing with normolipidemics. LDL receptor (LDLR) dysfunction and LDL-cholesterol (LDL-C) accumulation disturb the metabolism of other lipoprotein classes, such as chylomicrons and remnants and HDL. Read More

J Am Coll Cardiol 2014 May 12;63(19):1935-47. Epub 2014 Mar 12.

Section of Cardiovascular Disease Prevention, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address:

The severe hypercholesterolemia phenotype includes all patients with marked elevation of low-density lipoprotein cholesterol (LDL-C) levels. The most common cause is autosomal dominant hypercholesterolemia, an inherited disorder caused by mutations either in LDL receptor, apolipoprotein B (APOB), or proprotein convertase subtilisin kexin type 9 (PCSK9) genes. However, it is now known that many subjects with severe inherited hypercholesterolemia have no defects in these genes. Read More