166 results match your criteria Low LDL Cholesterol Hypobetalipoproteinemia


Comparison of two polygenic risk score to identify non-monogenic primary hypocholesterolemias in a large cohort of Italian hypocholesterolemic subjects.

J Clin Lipidol 2022 May 8. Epub 2022 May 8.

Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), Università degli Studi di Palermo, Via del Vespro 129, 90127, Palermo, Italy; Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Via U. La Malfa 153, 90146, Palermo, Italy. Electronic address:

Background: Primary Hypobetalipoproteinemias (HBL) are a group of dominant and recessive monogenic genetic disorders caused by mutations in APOB, PCSK9, ANGPTL3, MTTP, Sar1b genes and characterized by plasma levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) below the 5 percentile of the distribution in a given population. Mutations in the candidate genes account only for a small proportion of subjects with HBL suggesting a role for a polygenic contribution to the low cholesterol phenotype.

Objective: To explore the complex genetic architecture of HBL we compared two polygenic risk scores in order to assess the role of the polygenic burden and the differences in the clinical phenotype between monogenic and polygenic HBL; we studied a cohort of 170 subjects with primary HBL referred over a 25-year period to 2 Italian reference centers have been studied. Read More

View Article and Full-Text PDF

Monogenic and polygenic causes of low and extremely low LDL-C levels in patients referred to specialty lipid clinics: Genetics of low LDL-C.

J Clin Lipidol 2021 Sep-Oct;15(5):658-664. Epub 2021 Jul 17.

Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5323 Harry Hines Blvd, MC 8537, Dallas, TX 75390, United States. Electronic address:

Background: In clinical setting, current standard-of-care does not include genetic testing for patients with low (<50 mg/dL) and extremely low (<20 mg/dL) levels of serum low-density lipoprotein-cholesterol (LDL-C).

Objective: We aimed identify the underlying molecular cause - both monogenic and polygenic - of low and extremely low LDL-C levels in a cohort of patients presenting to specialty lipid clinics.

Methods: Whole exome sequencing was done in patients with low or extremely low LDL-C not due to any secondary causes. Read More

View Article and Full-Text PDF

Current Diagnosis and Management of Abetalipoproteinemia.

J Atheroscler Thromb 2021 Oct 16;28(10):1009-1019. Epub 2021 May 16.

Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center Research Institute.

Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by biallelic pathogenic mutations in the MTTP gene. Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia. Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy. Read More

View Article and Full-Text PDF
October 2021

Interrogation of selected genes influencing serum LDL-Cholesterol levels in patients with well characterized NAFLD.

J Clin Lipidol 2021 Mar-Apr;15(2):275-291. Epub 2020 Dec 27.

Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address:

Background: The clinical significance of rare mutations in LDL metabolism genes on nonalcoholic fatty liver disease (NAFLD) severity is not well understood.

Objective: To examine the significance of mutations in LDL metabolism genes including apolipoprotein B (APOB), proprotein convertase subtilisin kexin 9 (PCSK9) and LDL receptor (LDLR) in patients with NAFLD.

Methods: Patients with biopsy-confirmed NAFLD from the NASH Clinical Research Network studies were stratified into 3 groups of LDL-C (≤50 mg/dL, 130-150 mg/dL, ≥ 190 mg/dL) and then 120 (40 per group) were randomly selected from the strata. Read More

View Article and Full-Text PDF
December 2021

Phenotypic Differences Between Polygenic and Monogenic Hypobetalipoproteinemia.

Arterioscler Thromb Vasc Biol 2021 01 19;41(1):e63-e71. Epub 2020 Nov 19.

Hospices Civils de Lyon, UF Dyslipidémies Service de Biochimie et de Biologie Moléculaire Grand Est, Bron, France (X.V., D.C., O.M., E.D., M.D.F.).

Objective: Primary hypobetalipoproteinemia is characterized by LDL-C (low-density lipoprotein cholesterol) concentrations below the fifth percentile. Primary hypobetalipoproteinemia mostly results from heterozygous mutations in the (apolipoprotein B) and genes, and a polygenic origin is hypothesized in the remaining cases. Hypobetalipoproteinemia patients present an increased risk of nonalcoholic fatty liver disease and steatohepatitis. Read More

View Article and Full-Text PDF
January 2021

A Novel Variant in Gene Causes Extremely Low LDL-C Without Known Adverse Effects.

JACC Case Rep 2020 May 20;2(5):775-779. Epub 2020 May 20.

University of Michigan, Michigan Medicine, Ann Arbor, Michigan.

A novel frameshift variant was identified in that segregates in a dominant manner with low levels of low-density lipoprotein cholesterol. Affected family members show no apparent clinical complications. There is no consensus regarding clinical management, and the long-term consequences of low levels of low-density lipoprotein cholesterol remain unknown. Read More

View Article and Full-Text PDF

A Healthy Family of Familial Hypobetalipoproteinemia Caused by a Protein-truncating Variant in the PCSK9 Gene.

Intern Med 2020 15;59(6):783-787. Epub 2020 Mar 15.

Department of Cardiology, Kanazawa University Graduate School of Medicine, Japan.

We present the first case of a Japanese patient with familial hypobetalipoproteinemia (FHBL) caused by a protein-truncating variant in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene. A 34-year-old woman was referred to our hospital due to her low low-density lipoprotein (LDL)-cholesterolemia (34 mg/dL). She did not have any secondary causes of hypobetalipoproteinemia. Read More

View Article and Full-Text PDF

Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease.

Authors:
Francine K Welty

Curr Opin Lipidol 2020 04;31(2):49-55

Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Purpose Of Review: Several mutations in the apolipoprotein (apo) B, proprotein convertase subtilisin kexin 9 (PCSK9) and microsomal triglyceride transfer protein genes result in low or absent levels of apoB and LDL cholesterol (LDL-C) in plasma which cause familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia (ABL). Mutations in the angiopoietin-like protein 3 ANGPTL3 gene cause familial combined hypolipidemia (FHBL2). Clinical manifestations range from none-to-severe, debilitating and life-threatening disorders. Read More

View Article and Full-Text PDF

Low LDL cholesterol-Friend or foe?

J Clin Lipidol 2019 May - Jun;13(3):367-373. Epub 2019 May 16.

Department of Pediatric Endocrinology, Cook Children's Medical Center, Ft Worth, TX, USA. Electronic address:

View Article and Full-Text PDF

N-Glycosylation Defects in Humans Lower Low-Density Lipoprotein Cholesterol Through Increased Low-Density Lipoprotein Receptor Expression.

Circulation 2019 07 23;140(4):280-292. Epub 2019 May 23.

Departments of Vascular Medicine (M.A.W.v.d.B., J.K., G.M.D.-T., E.S.G.S., A.G.H.), Amsterdam University Medical Centers, location AMC, The Netherlands.

Background: The importance of protein glycosylation in regulating lipid metabolism is becoming increasingly apparent. We set out to further investigate this by studying patients with type I congenital disorders of glycosylation (CDGs) with defective N-glycosylation.

Methods: We studied 29 patients with the 2 most prevalent types of type I CDG, ALG6 (asparagine-linked glycosylation protein 6)-deficiency CDG and PMM2 (phosphomannomutase 2)-deficiency CDG, and 23 first- and second-degree relatives with a heterozygous mutation and measured plasma cholesterol levels. Read More

View Article and Full-Text PDF

Rare Protein-Truncating Variants in APOB, Lower Low-Density Lipoprotein Cholesterol, and Protection Against Coronary Heart Disease.

Circ Genom Precis Med 2019 05;12(5):e002376

Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (A.V.K., M.C., S.K.).

Background Familial hypobetalipoproteinemia is a genetic disorder caused by rare protein-truncating variants (PTV) in the gene encoding APOB (apolipoprotein B), the major protein component of LDL (low-density lipoprotein) and triglyceride-rich lipoprotein particles. Whether heterozygous APOB deficiency is associated with decreased risk for coronary heart disease (CHD) is uncertain. We combined family-based and large scale gene-sequencing to characterize the association of rare PTVs in APOB with circulating LDL-C (LDL cholesterol), triglycerides, and risk for CHD. Read More

View Article and Full-Text PDF

Extremely low levels of low-density lipoprotein potentially suggestive of familial hypobetalipoproteinemia: A separate phenotype of NAFLD?

J Clin Lipidol 2019 May - Jun;13(3):425-431. Epub 2019 Feb 14.

Division of Gastroenterology, Hepatology and Nutrition, University of Cincinnati School of Medicine, Cincinnati, OH, USA.

Background: Low-density lipoprotein cholesterol (LDL-C) levels below 50 mg/dL may suggest familial hypobetalipoproteinemia, particularly in patients with hepatic steatosis. The prevalence of hypobetalipoproteinemia in cohorts with nonalcoholic fatty liver disease (NAFLD) is not known, and it is not clear whether the severity of liver disease of these patients is different. The objective of this study was to address these questions in a large pediatric NAFLD cohort. Read More

View Article and Full-Text PDF

Molecular analysis of APOB, SAR1B, ANGPTL3, and MTTP in patients with primary hypocholesterolemia in a clinical laboratory setting: Evidence supporting polygenicity in mutation-negative patients.

Atherosclerosis 2019 04 11;283:52-60. Epub 2019 Feb 11.

Hospital de la Santa Creu i Sant Pau, Servei de Bioquímica - IIB Sant Pau, Barcelona, Spain. Electronic address:

Background And Aims: Primary hypobetalipoproteinemia is generally considered a heterogenic group of monogenic, inherited lipoprotein disorders characterized by low concentrations of LDL cholesterol and apolipoprotein B in plasma. Lipoprotein disorders include abetalipoproteinemia, familial hypobetalipoproteinemia, chylomicron retention disease, and familial combined hypolipidemia. Our aim was to review and analyze the results of the molecular analysis of hypolipidemic patients studied in our laboratory over the last 15 years. Read More

View Article and Full-Text PDF

Prevalence of hypobetalipoproteinemia and related psychiatric characteristics in a psychiatric population: results from the retrospective HYPOPSY Study.

Lipids Health Dis 2018 Nov 6;17(1):249. Epub 2018 Nov 6.

CHU Nantes, Service d'Addictologie et de Psychiatrie, F-44000, Nantes, France.

Background: Hypobetalipoproteinemia (HBL) is defined by plasma concentrations of LDL-cholesterol (LDL-C) lower than the fifth percentile for age and sex. Several psychiatric symptoms have been reported in association with HBL. The objective was to assess the prevalence of primary HBL in patients hospitalized in a psychiatric population and to better characterize the related psychiatric disorders. Read More

View Article and Full-Text PDF
November 2018

Genetics, Lifestyle, and Low-Density Lipoprotein Cholesterol in Young and Apparently Healthy Women.

Circulation 2018 02;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

View Article and Full-Text PDF
February 2018

Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels.

PLoS One 2017 16;12(10):e0186446. Epub 2017 Oct 16.

Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Background: Screening of variants, related to lipid metabolism in patients with extreme cholesterol levels, is a tool used to identify targets affecting cardiovascular outcomes. The aim of this study was to examine the prevalence and characteristics of rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol (LDL-C) levels.

Methods: Among 13,545 participants enrolled in a cardiovascular genome cohort, 22 subjects, whose LDL-C levels without lipid-lowering agents were ≤1 percentile (48 mg/dL) of Korean population, were analyzed. Read More

View Article and Full-Text PDF
November 2017

Threshold Effects of Circulating Angiopoietin-Like 3 Levels on Plasma Lipoproteins.

J Clin Endocrinol Metab 2017 09;102(9):3340-3348

Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon 97239.

Context: Angiopoietin-like 3 (ANGPTL3) deficiency in plasma due to loss-of-function gene mutations results in familial combined hypobetalipoproteinemia type 2 (FHBL2) in homozygotes. However, the lipid phenotype in heterozygotes is much milder and does not appear to relate directly to ANGPTL3 levels. Furthermore, the low-density lipoprotein (LDL) phenotype in carriers of ANGPTL3 mutations is unexplained. Read More

View Article and Full-Text PDF
September 2017

Low-Density Lipoprotein Cholesterol (LDL-C): How Low?

Authors:
Thomas F Whayne

Curr Vasc Pharmacol 2017 ;15(4):374-379

Wethington Building, 900 South Limestone Street, Lexington, KY 40536-0200. United States.

Low-density lipoprotein cholesterol (LDL-C) is a well-established major cardiovascular (CV) risk factor supported by clinical evidence showing decreased atherosclerotic disease events when LDL-C is therapeutically lowered. A reasonable approach is to tailor each patient's LDL-C target level depending on the initial LDL-C level and the perceived risk. Multiple clinical entities such as the newborn, hypobetalipoproteinemia, proprotein convertase subtilisin/kexin type 9 (PCSK9) missense mutations, and an unexpected excess response to a statin or other medications, are associated with very low LDL-C levels in otherwise healthy individuals. Read More

View Article and Full-Text PDF

Association between familial hypobetalipoproteinemia and the risk of diabetes. Is this the other side of the cholesterol-diabetes connection? A systematic review of literature.

Acta Diabetol 2017 Feb 2;54(2):111-122. Epub 2016 Nov 2.

Department of Biomedicine, Internal Medicine and Medical Specialties (DIBIMIS), University of Palermo, Palermo, Italy.

Statin therapy is beneficial in reducing LDL cholesterol (LDL-C) levels and cardiovascular events, but it is associated with the risk of incident diabetes mellitus (DM). Familial hypercholesterolemia (FH) is characterized by genetically determined high levels of plasma LDL-C and a low prevalence of DM. LDL-C levels seem then inversely correlated with prevalence of DM. Read More

View Article and Full-Text PDF
February 2017

 The relation of fibrosis stage with nutritional deficiencies and bioelectrical impedance analysis of body composition in patients with chronic hepatitis C.

Ann Hepatol 2016 Jul-Aug;15(4):492-500

Services of Gastroenterology Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Department of Medicine, Medical School, Universidad Complutense, Madrid, Spain.

Unlabelled:  Background. Nutritional deficiencies may aggravate the course of chronic hepatitis C (CHC). Our aim has been to perform a comprehensive analysis of body composition and nutritional deficiencies in CHC patients in non-cirrhotic and compensated cirrhotic stages to correlate the detected deficiencies with the fibrosis stage. Read More

View Article and Full-Text PDF
February 2017

Novel APOB missense variants, A224T and V925L, in a black South African woman with marked hypocholesterolemia.

J Clin Lipidol 2016 May-Jun;10(3):604-9. Epub 2016 Feb 16.

School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital, Perth, Western Australia, Australia. Electronic address:

Background: One genetic cause of markedly low plasma concentrations of apolipoprotein (apo) B and low density lipoprotein (LDL)-cholesterol is familial hypobetalipoproteinemia.

Objective: We aimed to determine the molecular basis for the marked hypocholesterolemia consistent with heterozygous familial hypobetalipoproteinemia in a black female subject of Xhosa lineage.

Methods: Coding regions of APOB, MTTP, PCSK9,ANGPTL3, SAR1B and APOC3 were sequenced, and APOE was genotyped. Read More

View Article and Full-Text PDF
October 2017

Identification of novel APOB mutations by targeted next-generation sequencing for the molecular diagnosis of familial hypobetalipoproteinemia.

Atherosclerosis 2016 07 11;250:52-6. Epub 2016 Apr 11.

INSERM, UMR1087, l'institut du thorax, Nantes, F-44000, France; CNRS, UMR 6291, Nantes, F-44000, France; Université de Nantes, Nantes, F-44000, France; CHU Nantes, l'institut du Thorax, Nantes, F-44000, France; CIC Thorax, CHU Nantes, l'institut du Thorax, Nantes, F-44000, France. Electronic address:

Background And Aims: Familial hypobetalipoproteinemia (FHBL) is a co-dominant disorder characterized by decreased plasma levels of LDL-cholesterol and apolipoprotein B (ApoB). Currently, genetic diagnosis in FHBL relies largely on Sanger sequencing to identify APOB and PCSK9 gene mutations and on western blotting to detect truncated ApoB species.

Methods: Here, we applied targeted enrichment and next-generation sequencing (NGS) on a panel of three FHBL genes and two abetalipoproteinemia genes (APOB, PCSK9, ANGPTL3, MTTP and SAR1B). Read More

View Article and Full-Text PDF

Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia.

Dis Model Mech 2016 Jan 19;9(1):81-90. Epub 2015 Nov 19.

INSERM, UMR1087, L'institut du thorax, Nantes F-44000, France CNRS, UMR 6291, Nantes F-44000, France Université de Nantes, Nantes F-44000, France CHU Nantes, L'institut du thorax, CIC Endocrinology-Nutrition, Nantes F-44000, France.

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a critical modulator of cholesterol homeostasis. Whereas PCSK9 gain-of-function (GOF) mutations are associated with autosomal dominant hypercholesterolemia (ADH) and premature atherosclerosis, PCSK9 loss-of-function (LOF) mutations have a cardio-protective effect and in some cases can lead to familial hypobetalipoproteinemia (FHBL). However, limitations of the currently available cellular models preclude deciphering the consequences of PCSK9 mutation further. Read More

View Article and Full-Text PDF
January 2016

Update on the molecular biology of dyslipidemias.

Authors:
I Ramasamy

Clin Chim Acta 2016 Feb 4;454:143-85. Epub 2015 Nov 4.

Department of Biochemistry, Worcester Royal Hospital, Worcester, United Kingdom.

Dyslipidemia is a commonly encountered clinical condition and is an important determinant of cardiovascular disease. Although secondary factors play a role in clinical expression, dyslipidemias have a strong genetic component. Familial hypercholesterolemia is usually due to loss-of-function mutations in LDLR, the gene coding for low density lipoprotein receptor and genes encoding for proteins that interact with the receptor: APOB, PCSK9 and LDLRAP1. Read More

View Article and Full-Text PDF
February 2016

Lipoprotein Metabolism in APOB L343V Familial Hypobetalipoproteinemia.

J Clin Endocrinol Metab 2015 Nov 31;100(11):E1484-90. Epub 2015 Aug 31.

Department of Clinical Biochemistry (A.J.H., L.H., K.R., F.M.v.B., J.R.B.), PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth WA 6000, Australia; School of Medicine and Pharmacology (A.J.H., D.C., P.H.R.B., J.R.B.), and School of Pathology and Laboratory Medicine (A.J.H., K.R.), University of Western Australia, Crawley WA 6009, Australia; Department of Radiology (J.H., S.S.), Royal Perth Hospital, Perth WA 6000, Australia; Medical Department II (K.G.P.), Grosshadern, University of Munich, 81377 Munich, Germany; and School of Surgery (F.M.v.B.), University of Western Australia, Crawley WA 6009, Australia.

Context: Familial hypobetalipoproteinemia (FHBL) is a codominant disorder of lipoprotein metabolism characterized by decreased plasma concentrations of low-density lipoprotein (LDL)-cholesterol and apolipoprotein B (apoB).

Objective: The objective was to examine the effect of heterozygous APOB L343V FHBL on postprandial triglyceride-rich lipoprotein (TRL) and fasting lipoprotein metabolism.

Methods: Plasma incremental area under the curve apoB-48 and apoB-48 kinetics were determined after ingestion of a standardized oral fat load using compartmental modeling. Read More

View Article and Full-Text PDF
November 2015

Homozygous familial hypobetalipoproteinemia: two novel mutations in the splicing sites of apolipoprotein B gene and review of the literature.

Atherosclerosis 2015 Mar 19;239(1):209-17. Epub 2015 Jan 19.

Department of Pharmacology and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy; IRCCS Multimedica, Milano, Italy. Electronic address:

Objective: Familial hypobetalipoproteinemia (FHBL) is autosomal codominant disorder of lipoprotein metabolism characterized by low plasma levels of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) below the 5(th) percentile of the distribution in the population. Patients with the clinical diagnosis of homozygous FHBL (Ho-FHBL) are extremely rare and few patients have been characterized at the molecular level. Here we report the medical history and the molecular characterization of one paediatric patient with clinical features of Ho-FHBL. Read More

View Article and Full-Text PDF

Contemporary aspects of the biology and therapeutic regulation of the microsomal triglyceride transfer protein.

Circ Res 2015 Jan;116(1):193-205

Department of Clinical Biochemistry, PathWest Laboratory Medicine WA (A.J.H., J.R.B.), School of Medicine and Pharmacology (A.J.H., J.R.B., G.F.W.), School of Pathology and Laboratory Medicine (A.J.H), and Lipid Disorders Clinic, Cardiovascular Medicine (J.R.B., G.F.W), Royal Perth Hospital, University of Western Australia, Perth, Western Australia, Australia.

The microsomal triglyceride transfer protein (MTP), the product of the MTTP gene, is essential for the assembly and secretion of apolipoprotein B-containing lipoproteins, but when defective causes abetalipoproteinemia. Abetalipoproteinemia is a rare autosomal recessive disorder characterized by the inability to produce chylomicrons or very low-density lipoproteins, with the absence of apolipoprotein B-containing lipoproteins in the circulation. Knowledge of the molecular basis for abetalipoproteinemia has led to the development of therapies for dyslipidemia that inhibit MTP. Read More

View Article and Full-Text PDF
January 2015

Hypobetalipoproteinemia and abetalipoproteinemia.

Authors:
Francine K Welty

Curr Opin Lipidol 2014 Jun;25(3):161-8

Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Purpose Of Review: Several mutations in the apoB, proprotein convertase subtilisin/kexin type 9 (PCSK9), and MTP genes result in low or absent levels of apoB and LDL-cholesterol in plasma, which cause familial hypobetalipoproteinemia and abetalipoproteinemia. Mutations in the ANGPTL3 gene cause familial combined hypolipidemia. Clinical manifestations range from none to severe, debilitating, and life-threatening disorders. Read More

View Article and Full-Text PDF