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Curr Atheroscler Rep 2020 Jun 18;22(8):32. Epub 2020 Jun 18.

Section of Cardiology, Baylor College of Medicine, Houston, TX, USA.

Purpose Of Review: The review highlights selected studies related to cardiovascular disease (CVD) prevention that were presented at the American College of Cardiology 2020 Virtual Scientific Session (ACC.20)/World Cardiology Congress (WCC).

Recent Findings: The studies reviewed include clinical trials on the efficacy and safety of alirocumab (Study in Participants with Homozygous Familial Hypercholesterolemia [ODYSSEY HoFH]) and evinacumab in the treatment of homozygous familial hypercholesterolemia (HoFH); Evaluating the Efficacy of E-cigarettes for Smoking Cessation (E3); the use of renal denervation in the treatment of hypertension (SPYRAL HTN-OFF MED PIVOTAL); and the assessment of vericiguat in the treatment of heart failure (A Study of Vericiguat in Participants with Heart Failure with Reduce Ejection Fraction [VICTORIA]). Read More

Curr Opin Lipidol 2020 Jun 8. Epub 2020 Jun 8.

Departments of Biochemistry and Medicine, and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

Purpose Of Review: The aim of this study was to evaluate the potential role of genetic testing, particularly next-generation DNA sequencing, in diagnosing and managing dyslipidaemias, particularly monogenic dyslipidaemias.

Recent Findings: Targeted DNA sequencing of the genes causing monogenic dyslipidaemias is becoming more accessible. Some societies' position statements advise selective utilization of DNA testing in combination with clinical and biochemical assessment. Read More

J Clin Lipidol 2020 May 7. Epub 2020 May 7.

Professor of Medicine and Biochemistry, Department of Medicine and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. Electronic address:

The genetic basis for more than 2 dozen monogenic dyslipidemias has largely been defined. Genetic technologies, such as DNA sequencing, can detect both rare and common DNA variants underlying dyslipidemias, and these methods are increasingly available. Although patients with extreme abnormalities in low-density lipoprotein cholesterol, triglycerides, or high-density lipoprotein cholesterol may be considered for genetic testing, it is only in a minority of patients that the results will alter treatment or outcomes. Read More

Arch Cardiol Mex 2020 ;90(2):151-157

Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Laboratorio de Lípidos y Aterosclerosis, Universidad de Buenos Aires, Buenos Aires, Argentina.

Objective: Familial hypercholesterolemia (FH) is a monogenic disease, associated with variants in the LDLR, APOB and PCSK9 genes. The initial diagnosis is based on clinical criteria like the DLCN criteria. A score > 8 points qualifies the patient as "definite" for FH diagnosis. Read More

Atherosclerosis 2020 May 16. Epub 2020 May 16.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Life (Basel) 2020 May 20;10(5). Epub 2020 May 20.

Department of Cardiology I, Medical University of Gdansk, Dębinki 7, 80-211 Gdańsk, Poland.

Background The monogenic defect in familial hypercholesterolemia (FH) is detected in ∼40% of cases. The majority of mutation-negative patients have a polygenic cause of high LDL-cholesterol (LDL-C). We sought to investigate whether the underlying monogenic or polygenic defect is associated with the response to rosuvastatin. Read More

Curr Opin Lipidol 2020 Jun;31(3):111-118

Imperial Centre for Cardiovascular Disease Prevention (ICCP), Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK.

Purpose Of Review: This review explores the concepts of monogenic and the so-called polygenic familial hypercholesterolemia and how the identification of familial hypercholesterolemia as a monogenic condition and its separation from polygenic primary hypercholesterolemia may have implications for clinical practice.

Recent Findings: Through genetic testing, a mutation in any of the three known autosomal dominant familial hypercholesterolemia-causing genes is found in 60-80% of cases with a clinical diagnosis of definite familial hypercholesterolemia. As individuals with a polygenic basis for their hypercholesterolemia do not follow the same inheritance pattern observed in monogenic familial hypercholesterolemia, the use of family-based cascade screening in individuals with a polygenic origin is not recommend, as only 30% of relatives have an elevated LDL-C compared to the 50% in monogenic families. Read More

Mol Genet Genomic Med 2020 Jun 19;8(6):e1248. Epub 2020 Apr 19.

Department of Life Sciences, Centre for Integrative Systems Biology and Bioinformatics, Imperial College London, London, United Kingdom.

Background: Severe hypercholesterolemia (HC, LDL-C > 4.9 mmol/L) affects over 30 million people worldwide. In this study, we validated a new polygenic risk score (PRS) for LDL-C. Read More

Pharmgenomics Pers Med 2020 2;13:59-70. Epub 2020 Mar 2.

Center for Research in Genetics and Genomics-CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences. Universidad Del Rosario, Bogotá, Colombia.

Rosuvastatin, is a widely-used statin for the treatment of hypercholesterolemia and the prevention of cardiovascular diseases. Although rosuvastatin is well tolerated, about 3/10.000 patients can suffer severe myopathy. Read More

CJC Open 2019 May 15;1(3):115-118. Epub 2019 Mar 15.

Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

Background: Inhibitors of proprotein convertase subtilisin kexin 9 are indicated in Canada for treatment of patients with familial hypercholesterolemia (FH). Classically, FH is considered to be a monogenic condition caused by rare pathogenic mutations; however, some patients have hypercholesterolemia on a polygenic basis. Whether the effect of proprotein convertase subtilisin kexin 9 inhibitor treatment differs between patients with monogenic hypercholesterolemia and patients with polygenic hypercholesterolemia is unclear. Read More

Circ Genom Precis Med 2020 Apr 10;13(2):e002725. Epub 2020 Mar 10.

Institute for Molecular Medicine Finland, Helsinki Institute of Life Science (HiLIFE) (P.R., J.T.R., N.J.M., Y.F., J.L., C.B., I.S., T.K., A.S.H., P.P., E.W., T.T., M.P., A.P., S.R.), University of Helsinki, Helsinki, Finland.

Background: Hyperlipidemia is a highly heritable risk factor for coronary artery disease (CAD). While monogenic familial hypercholesterolemia associates with severely increased CAD risk, it remains less clear to what extent a high polygenic load of a large number of LDL (low-density lipoprotein) cholesterol (LDL-C) or triglyceride (TG)-increasing variants associates with increased CAD risk.

Methods: We derived polygenic risk scores (PRSs) with ≈6M variants separately for LDL-C and TG with weights from a UK Biobank-based genome-wide association study with ≈324K samples. Read More

Anatol J Cardiol 2020 02;23(3):120-127

Advanced Center for Medical and Pharmaceutical Research, University of Medicine, Pharmacy, Science and Technology of Targu Mures; Targu Mures-Romania.

Familial hypercholesterolemia (FH) is considered the genetic cause of coronary heart disease and ischemic stroke. FH is mainly an autosomal codominant pattern-based disorder and is primarily determined by point mutations within the low-density lipoprotein receptor, apolipoprotein B, and proprotein convertase subtilisin/kexin type 9 genes, causing increased low-density lipoprotein cholesterol levels in the serum of untreated individuals. The accumulation will eventually lead to atherosclerotic cardiovascular disease. Read More

Curr Opin Cardiol 2020 May;35(3):226-233

Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital.

Purpose Of Review: With the exception of familial hypercholesterolaemia, the value of genetic testing for managing dyslipidaemias is not established. We review the genetics of major dyslipidaemias in context of clinical practice.

Recent Findings: Genetic testing for familial hypercholesterolaemia is valuable to enhance diagnostic precision, cascade testing, risk prediction and the use of new medications. Read More

JAMA Cardiol 2020 Feb 12. Epub 2020 Feb 12.

Centre for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada.

Importance: Monogenic familial hypercholesterolemia (FH) is associated with lifelong elevations in low-density lipoprotein cholesterol (LDL-C) levels and increased risk of atherosclerotic cardiovascular disease (CVD). However, many individuals with hypercholesterolemia have a polygenic rather than a monogenic cause for their condition. It is unclear if a genetic variant for hypercholesterolemia alters the risk of CVD. Read More

BMC Med Genomics 2020 02 10;13(1):23. Epub 2020 Feb 10.

Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond St, London, ON, N6A 5B7, Canada.

Background: In 2013, our laboratory designed a targeted sequencing panel, "LipidSeq", to study the genetic determinants of dyslipidemia and metabolic disorders. Over the last 6 years, we have analyzed 3262 patient samples obtained from our own Lipid Genetics Clinic and international colleagues. Here, we highlight our findings and discuss research benefits and clinical implications of our panel. Read More

J Clin Endocrinol Metab 2020 Jun;105(6)

Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Context: As many as 75% of patients with polycystic ovary syndrome (PCOS) are estimated to be unidentified in clinical practice.

Objective: Utilizing polygenic risk prediction, we aim to identify the phenome-wide comorbidity patterns characteristic of PCOS to improve accurate diagnosis and preventive treatment.

Design, Patients, And Methods: Leveraging the electronic health records (EHRs) of 124 852 individuals, we developed a PCOS risk prediction algorithm by combining polygenic risk scores (PRS) with PCOS component phenotypes into a polygenic and phenotypic risk score (PPRS). Read More

Clin Genet 2020 Mar;97(3):457-466

Cardiovascular Research Group, Research and Development Unit, Department of Health Promotion and Chronic Diseases, National Institute of Health Doutor Ricardo Jorge, Lisbon, Portugal.

Familial hypercholesterolaemia (FH) is a monogenic disorder characterised by high low-density lipoprotein cholesterol (LDL-C) concentrations and increased cardiovascular risk. However, in clinically defined FH cohorts worldwide, an FH-causing variant is only found in 40%-50% of the cases. The aim of this work was to characterise the genetic cause of the FH phenotype in Portuguese clinical FH patients. Read More

Clin Genet 2020 Apr 27;97(4):543-555. Epub 2019 Dec 27.

School of Medicine, Faculty of Medicine and Health Sciences, The University of Western Australia, Perth, Australia.

Familial hypercholesterolaemia (FH) is caused by pathogenic variants in LDLR, APOB or PCSK9. Impaired low-density lipoprotein (LDL) receptor function leads to decreased LDL catabolism and premature atherosclerotic cardiovascular disease (ASCVD). Thousands of LDLR variants are known, but assignation of pathogenicity requires accurate phenotyping, family studies and assessment of LDL receptor function. Read More

Cardiovasc J Afr 2019 Sep/Oct;30(5):297-304

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

Familial hypercholesterolaemia (FH) is a common autosomal dominantly inherited disorder in which impaired clearance of plasma low-density lipoprotein cholesterol causes premature atherosclerotic vascular disease and tendon xanthomata. This workshop aimed to consolidate information on the diagnosis and management of FH in South Africa. The genetic causes include mutations in the LDL receptor, apolipoprotein B100 and proprotein convertase subtilisin/kexin type 9 (PCSK9). Read More

J Med Food 2020 Jun 30;23(6):658-666. Epub 2019 Oct 30.

IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

The guidelines for the treatment of dyslipidemias include the use of nutraceuticals (NUTs) in association with lifestyle modifications to achieve therapeutic goals. In NUT pill, different substances may be associated; in this study we investigated a combined NUT containing monacolin K (MonK)+KA (1:1), berberine (BBR), and silymarin. The aim of the study was to evaluate low-density lipoprotein cholesterol (LDL-C) reduction in 53 patients suffering from polygenic hypercholesterolemia, characterized by a low/intermediate cardiovascular risk calculated with SCORE algorithm. Read More

Nat Commun 2019 10 25;10(1):4897. Epub 2019 Oct 25.

Geisinger Health System, Danville, PA, USA.

Rare genetic disorders (RGDs) often exhibit significant clinical variability among affected individuals, a disease characteristic termed variable expressivity. Recently, the aggregate effect of common variation, quantified as polygenic scores (PGSs), has emerged as an effective tool for predictions of disease risk and trait variation in the general population. Here, we measure the effect of PGSs on 11 RGDs including four sex-chromosome aneuploidies (47,XXX; 47,XXY; 47,XYY; 45,X) that affect height; two copy-number variant (CNV) disorders (16p11. Read More

JAMA Netw Open 2019 10 2;2(10):e1913491. Epub 2019 Oct 2.

Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine in St Louis, St Louis, Missouri.

Importance: Acquired and heritable traits are associated with dementia risk; however, how these traits are associated with age at symptomatic onset (AAO) of Alzheimer disease (AD) is unknown. Identifying the associations of acquired and heritable factors with variability in intergenerational AAO of AD could facilitate diagnosis, assessment, and counseling of the offspring of parents with AD.

Objective: To quantify the associations of acquired and heritable factors with intergenerational differences in AAO of AD. Read More

Lancet Diabetes Endocrinol 2019 11 21;7(11):880-886. Epub 2019 Aug 21.

Departments of Medicine and Physiology, Division of Endocrinology and Metabolism, Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, Canada. Electronic address:

Diagnostic scoring systems for familial hypercholesterolaemia and familial chylomicronaemia syndrome often cannot differentiate between adults who have extreme dyslipidaemia based on a simple monogenic cause versus people with a more complex cause involving polygenic factors and an environmental component. This more complex group of patients carries a substantial risk of atherosclerotic cardiovascular disease in the case of marked hypercholesterolaemia and pancreatitis in the case of marked hypertriglyceridaemia. Complications are mainly a function of the degree of disturbance in lipid metabolism resulting in elevated lipid levels, so the added value of knowing the precise genetic cause in clinical decision making is unclear and does not lead to clinically meaningful benefit. Read More

Curr Opin Cardiol 2019 11;34(6):706-713

Population Health Research Institute.

Purpose Of Review: This review is a comprehensive update on recent discoveries on the genetics of early-onset coronary artery disease (EOCAD), and how those findings can be translated to advance its medical management.

Recent Findings: To date, a total of 266 common variants of modest effect size have been reported to be associated with CAD, but many still warrant functional studies. Rare variants impacting the function of at least 10 genes are now well characterized in Mendelian EOCAD. Read More

J Am Coll Cardiol 2019 07;74(4):523-525

Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

J Am Coll Cardiol 2019 07;74(4):512-522

Centre for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada; Experimental Medicine Program, University of British Columbia, Vancouver, British Columbia, Canada; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background: A pathogenic variant in LDLR, APOB, or PCSK9 can be identified in 30% to 80% of patients with clinically-diagnosed familial hypercholesterolemia (FH). Alternatively, ∼20% of clinical FH is thought to have a polygenic cause. The cardiovascular disease (CVD) risk associated with polygenic versus monogenic FH is unclear. Read More

Circ J 2019 08 20;83(9):1917-1924. Epub 2019 Jul 20.

Department of Cardiology, Kanazawa University Graduate School of Medicine.

Background: A substantial proportion of patients clinically diagnosed as having familial hypercholesterolemia (FH) do not manifest causative mutation(s) in the FH genes such asLDLR,APOB, andPCSK9. We aimed to evaluate the effect of rare and deleterious mutation(s) inABCG5/ABCG8on hyper-low-density lipoprotein (LDL) cholesterolemia in individuals who meet the clinical criteria for FH.Methods and Results:We compared the LDL cholesterol (LDL-C) values among 487 subjects with FH; the subjects were grouped according to the presence of mutation(s) in FH andABCG5/ABCG8genes. Read More

Curr Opin Lipidol 2019 08;30(4):300-306

Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.

Purpose Of Review: Familial hypercholesterolemia has long been considered a monogenic disorder. However, recent advances in genetic analyses have revealed various forms of this disorder, including polygenic and oligogenic familial hypercholesterolemia. We review the current understanding of the genetic background of this disease. Read More

Atherosclerosis 2019 08 20;287:89-92. Epub 2019 Jun 20.

Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain.

The introduction of singular therapies, such as proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), to lower high cholesterol levels requires better classification of patients eligible for intensive lipid lowering therapy. According to the European Medicines Administration, PCSK9i are recommended in primary prevention only in familial hypercholesterolemia (FH) patients. Therefore, an FH diagnosis is not simply an academic issue, because it has many clinical implications. Read More

Circ Genom Precis Med 2019 06 11;12(6):e002481. Epub 2019 Jun 11.

Montreal Heart Institute (F.W., K.S.L., A.L.-A., D.B., M.-P.D., J.-C.T., G.L.), Université de Montréal, Québec, Canada.

Background: Coronary artery disease (CAD) represents one of the leading causes of morbidity and mortality worldwide. Given the healthcare risks and societal impacts associated with CAD, their clinical management would benefit from improved prevention and prediction tools. Polygenic risk scores (PRS) based on an individual's genome sequence are emerging as potentially powerful biomarkers to predict the risk to develop CAD. Read More

Curr Opin Cardiol 2019 07;34(4):406-412

Department of Metabolic Medicine/Chemical Pathology, Queen's Hospital, Burton-on-Trent, Staffordshire, UK.

Purpose Of Review: Extensive work has gone into understanding the genetics of cardiovascular disease (CVD) and implicating genes involved in hyperlipidaemia. Translation into routine practise involves using genetic risk scores (GRS) to identify high-risk individuals in the general population. Some of these risk scores are beginning to disentangle the complex nature of CVD and inherited dyslipidaemias. Read More

Curr Cardiol Rep 2019 04 22;21(6):43. Epub 2019 Apr 22.

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

Purpose Of The Review: Identification of loci and common single-nucleotide polymorphisms (SNPs) that have modest effects on plasma lipids have been used to confirm or refute the causal role of lipid traits in the development of coronary heart disease (CHD), and as tools to identify individuals with polygenic hypercholesterolemia.

Recent Findings: Several groups have reported on the use of SNP scores in distinguishing individuals with a clinical diagnosis of familial hypercholesterolemia (FH) with a monogenic or polygenic etiology. We review evidence that those with monogenic FH have worse prognosis and discuss the possible mechanisms for this and their management. Read More

J Clin Lipidol 2019 May - Jun;13(3):411-414. Epub 2019 Mar 6.

Department of Medicine and Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.

We present a 37-year-old man diagnosed with familial dysbetalipoproteinemia who presented with the severe hyperlipidemic phenotype. None of the usual metabolic triggers were found to explain his severe lipid abnormalities. Genetic analysis revealed the expected APOE E2/E2 genotype, but no other mutations were found to explain any monogenic dyslipidemia or syndrome. Read More

Atheroscler Suppl 2019 Mar;36:28-30

Metabolic Unit, Pediatric Department, Santa Maria Hospital, Lisboa, Portugal.

Familial hypercholesterolemia is an Mendelian dominant disorder characterized by defects of the low density lipoprotein receptor (LDLR) that result in a defective removal of LDL from plasma, which promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and arteries (atherosclerosis). Diagnosis severe clinical phenotype FH with Dutch Lipid Clinic Network Criteria, encompassing history of premature ASCVD, tendon xanthomas, and a family history of hypercholesterolemia and premature ASCVD in relatives is rare in the Portuguese FH patients. There is a variability of the phenotype in FH individuals with clinical diagnosis or genetic mutation (carriers and patients) probably due to environmental factors in the last century, a Mediterranean diet, or a diet without fat food, trans fat food, no smoking, no sedentary life that can interfere with our metabolism, or are consequences of polygenic, epigenetic, acquired defects, modifiers genes and beta-globin asymptomatic carriers. Read More

Trends Cardiovasc Med 2020 Jan 19;30(1):48-53. Epub 2019 Feb 19.

Department of Medicine (Cardiovascular Division) and Radiology, Brigham and Women's Hospital, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA. Electronic address:

HMG coenzyme A reductase inhibitors (statins) significantly decrease low-density lipoprotein-cholesterol, resulting in stabilization, and in some cases regression, of atherosclerotic plaque with subsequent reduction in atherosclerotic cardiovascular disease (ASCVD) events. To date, there remains a paucity of data to guide the use of statins in young adults (20-49 years old). We herein aim to summarize the potential benefits and risks for statin therapy in younger adults, outlining a possible approach to statin use in young adults. Read More

Front Cardiovasc Med 2019 29;6. Epub 2019 Jan 29.

Division of Cardiovascular Medicine and Cardiovascular Institute, Stanford University, Stanford, CA, United States.

Familial Hypercholesterolemia (FH) is an inherited lipid disorder affecting 1 in 220 individuals resulting in highly elevated low-density lipoprotein levels and risk of premature coronary disease. Pathogenic variants causing FH typically involve the LDL receptor (), apolipoprotein B-100 (), and proprotein convertase subtulisin/kexin type 9 genes () and if identified convey a risk of early onset coronary artery disease (ASCVD) of 3- to 10-fold vs. the general population depending on the severity of the mutation. Read More

Curr Opin Lipidol 2019 04;30(2):82-87

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

Purpose Of Review: To discuss the heterogeneity of atherosclerotic cardiovascular disease (ASCVD) risk in heterozygous familial hypercholesterolemia and evidence and limitations of clinical risk scores and subclinical coronary atherosclerosis (SCA) imaging to evaluate risk.

Recent Findings: Risk evaluation in contemporary familial hypercholesterolemia cohorts needs to consider the cause of the familial hypercholesterolemia phenotype, for example the presence of autosomal molecular defects that impart a greater ASCVD risk than in polygenic hypercholesterolemia, prospective follow-up and the impact of statin treatment. As atherosclerosis is multifactorial, clinical scores like the Montreal familial hypercholesterolemia score and SAFEHEART risk equation have been proposed to stratify ASCVD in statin-treated, molecularly defined familial hypercholesterolemia individuals. Read More

Circulation 2019 03;139(13):1593-1602

Center for Genomic Medicine (A.V.K., R.L.C., M.E.T., S.K.), Massachusetts General Hospital, Boston.

Background: The relative prevalence and clinical importance of monogenic mutations related to familial hypercholesterolemia and of high polygenic score (cumulative impact of many common variants) pathways for early-onset myocardial infarction remain uncertain. Whole-genome sequencing enables simultaneous ascertainment of both monogenic mutations and polygenic score for each individual.

Methods: We performed deep-coverage whole-genome sequencing of 2081 patients from 4 racial subgroups hospitalized in the United States with early-onset myocardial infarction (age ≤55 years) recruited with a 2:1 female-to-male enrollment design. Read More

Pathology 2019 Feb 14;51(2):184-192. Epub 2018 Dec 14.

Departments of Medicine and Biochemistry, and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. Electronic address:

Dyslipidaemias encompass about two dozen relatively rare monogenic disorders and syndromes for which the genetic basis has largely been defined. In addition, the complex polygenic basis of disturbed lipids and lipoproteins has been characterised in many patients, and has been shown to result from accumulation of many common polymorphisms with small effects on lipids. Genetic technologies, including dedicated genotyping and sequencing methods can detect both rare and common DNA variants underlying dyslipidaemias. Read More

Am J Cardiol 2019 02 23;123(4):588-591. Epub 2018 Nov 23.

Department of Medical and Surgical Sciences, Alma Mater Studiorum - Università di Bologna, Bologna, Italy.

Hypercholesterolemia represents one of the main reversible cardiovascular risk factors. In this pilot clinical trial, we have tested the short-term efficacy and safety of a new combined cholesterol-lowering nutraceutical containing artichoke dry extract and berberine at enhanced bioavailability in subjects with moderate polygenic hypercholesterolemia in primary prevention for cardiovascular disease. After 2 months of treatment, the tested nutraceutical induced a significant reduction in plasma total cholesterol (-19%), low-density lipoprotein cholesterol (-16%), non-high-density lipoprotein cholesterol (-19%) and triglyceride levels (-15%), in association with a standardized control diet. Read More

Praxis (Bern 1994) 2018 Nov;107(24):1345-1353

1 Klinik für Endokrinologie, Diabetologie, Osteologie und Stoffwechselkrankheiten, Kantonsspital St. Gallen.

Diagnosis and Treatment of Familial Hypercholesterolemia Abstract. Familial hypercholesterolemia secondary to heterozygous mutations in the LDL receptor, Apolipoprotein B or PCSK9 gene is characterized by 2- to 3-fold elevated LDL cholesterol levels, premature atherosclerosis and extravascular cholesterol deposits (tendon xanthomata, corneal arcus). The same phenotype may occur if a person carries several LDL cholesterol rising polymorphisms (polygenic FH). Read More

Transl Psychiatry 2018 10 12;8(1):218. Epub 2018 Oct 12.

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Bipolar disorder (BD) is a mental disorder characterized by alternating periods of depression and mania. Individuals with BD have higher levels of early mortality than the general population, and a substantial proportion of this is due to increased risk for comorbid diseases. To identify the molecular events that underlie BD and related medical comorbidities, we generated imputed whole-genome sequence data using a population-specific reference panel for an extended multigenerational Old Order Amish pedigree (n = 394), segregating BD and related disorders. Read More

J Clin Lipidol 2018 Nov - Dec;12(6):1452-1462. Epub 2018 Sep 7.

Institut de Recerca - Hospital de la Santa Creu i Sant Pau, Serveis de Bioquímica, i d'Endocrinologia i Nutrició, IIB Sant Pau, CIBERDEM, Universitat Autònoma de Barcelona, Departaments de Bioquímica i Biologia Molecular, i Medicina, Barcelona, Spain. Electronic address:

Background: Autosomal dominant hypercholesterolemia (ADH) is associated with mutations in the low-density lipoprotein (LDL) receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9) genes, and it is estimated to be greatly underdiagnosed. The most cost-effective strategy for increasing ADH diagnosis is a cascade screening from mutation-positive probands.

Objective: The objective of this study was to evaluate the results from 2008 to 2016 of ADH genetic analysis performed in our clinical laboratory, serving most lipid units of Catalonia, a Spanish region with approximately 7. Read More

Atherosclerosis 2018 10;277:457-463

Institute of Cardiovascular Science, University College London, 5 University St, London, WC1E 6JF, United Kingdom. Electronic address:

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. In the remainder, a polygenic aetiology may be the cause of the phenotype, due to the co-inheritance of common LDL-C raising variants. In 2013, we reported the development of a 12-SNP LDL-C "SNP-Score" based on common variants identified as LDL-C raising from genome wide association consortium studies, and have confirmed the validity of this score in samples of no-mutation FH adults and children from more than six countries with European-Caucasian populations. Read More

Atherosclerosis 2018 10;277:256-261

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, INFIBIOC-UBA, Buenos Aires, Argentina. Electronic address:

Background And Aims: Marked hypercholesterolemia, defined as low density lipoprotein cholesterol (LDL-C) levels ≥ 190 mg/dL, may be due to LDLR, APOB, and PCSK9 variants. In a recent analysis, only 1.7% of cases had such variants. Read More

J Clin Lipidol 2018 Nov - Dec;12(6):1436-1444. Epub 2018 Aug 23.

Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.

Background: The genetic background of severe familial hypercholesterolemia (FH) has yet to be determined.

Objective: We tested if genetic variants associated with low-density lipoprotein (LDL)-altering autosomal recessive diseases influenced LDL cholesterol levels and the odds for coronary artery disease in patients with high LDL cholesterol.

Methods: We recruited 500 individuals with elevated LDL cholesterol levels (≥180 mg/dL or ≥140 mg/dL for subjects <15 years). Read More

J Pers Med 2018 Aug 23;8(3). Epub 2018 Aug 23.

Department of Health Sciences Research (KRB), Mayo Clinic, Rochester, MN 55902, USA.

To inform guidelines for screening family members of patients with familial hypercholesterolemia (FH), we designed a clinical trial to compare the yield of cascade screening in FH patients with and without an identifiable pathogenic variant. Participants with hypercholesterolemia (Low-density lipoprotein cholesterol (LDL-C) > 155 mg/dL) underwent sequencing of , , and and genotyping of six single nucleotide polymorphisms associated with LDL-C followed by calculation of a polygenic score for LDL-C. We identified 24 patients with definite FH (pathogenic variant in one of the three FH genes), 76 patients with probable FH (Dutch lipid clinic network (DLCN) score ≥ 6, no pathogenic variant), and 262 patients with possible FH (DLCN score 3⁻5, no pathogenic variant). Read More

Nat Commun 2018 08 23;9(1):3391. Epub 2018 Aug 23.

Center for Genomic Medicine and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA.

Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Read More

Nat Rev Cardiol 2019 01;16(1):9-20

Departments of Medicine and Biochemistry, and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

Familial hypercholesterolaemia is the most commonly encountered genetic condition that predisposes individuals to premature cardiovascular disease. Nevertheless, most patients are undiagnosed, and treatment is often suboptimal even when the diagnosis seems certain. Advances in molecular technologies are reshaping our understanding of this condition, including revision upwards of the population prevalence. Read More