Dataset Information

Modern prevalence of dysbetalipoproteinemia (Fredrickson-Levy-Lees type III hyperlipoproteinemia).

ABSTRACT: Introduction:Dysbetalipoproteinaemia (HLP3) is a disorder characterized by excess cholesterol-enriched, triglyceride-rich lipoprotein remnants in genetically predisposed individuals that powerfully promote premature cardiovascular disease if untreated. The current prevalence of HLP3 is largely unknown. Material and methods:We performed cross-sectional analysis of 128,485 U.S. adults from the Very Large Database of Lipids (VLDbL), using four algorithms to diagnose HLP3 employing three Vertical Auto Profile ultracentrifugation (UC) criteria and a previously described apolipoprotein B (apoB) method. We evaluated 4,926 participants from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) with the apoB method. We examined demographic and lipid characteristics stratified by presence of HLP3 and evaluated lipid characteristics in those with HLP3 phenotype discordance and concordance as determined by apoB and originally defined UC criteria 1. Results:In U.S. adults in VLDbL and NHANES, a 1.7-2.0% prevalence is observed for HLP3 with the novel apoB method as compared to 0.2-0.8% prevalence in VLDbL via UC criteria 1-3. Participants who were both apoB and UC criteria HLP3 positive had higher remnant particles as well as more elevated triglyceride/apoB and total cholesterol/apoB ratios (all p < 0.001) than those who were apoB method positive and UC criteria 1 negative. Conclusions:HLP3 may be more prevalent than historically and clinically appreciated. The apoB method increases HLP3 identification via inclusion of milder phenotypes. Further work should evaluate the clinical implications of HLP3 diagnosis at various lipid algorithm cut-points to evaluate the ideal standard in the modern era.

SUBMITTER: Pallazola VA

PROVIDER: S-EPMC7444722 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Modern prevalence of dysbetalipoproteinemia (Fredrickson-Levy-Lees type III hyperlipoproteinemia).

Pallazola Vincent A VA Sathiyakumar Vasanth V Park Jihwan J Vakil Rachit M RM Toth Peter P PP Lazo-Elizondo Mariana M Brown Emily E Quispe Renato R Guallar Eliseo E Banach Maciej M Blumenthal Roger S RS Jones Steven R SR Marais David D Soffer Daniel D Sniderman Allan D AD Martin Seth S SS

Archives of medical science : AMS 20190802 5

<h4>Introduction</h4>Dysbetalipoproteinaemia (HLP3) is a disorder characterized by excess cholesterol-enriched, triglyceride-rich lipoprotein remnants in genetically predisposed individuals that powerfully promote premature cardiovascular disease if untreated. The current prevalence of HLP3 is largely unknown.<h4>Material and methods</h4>We performed cross-sectional analysis of 128,485 U.S. adults from the Very Large Database of Lipids (VLDbL), using four algorithms to diagnose HLP3 employing th ...[more]

PMID: 32863987

Similar Datasets

Project description:BackgroundApolipoprotein E (apoE) is a major protein of the lipoprotein transport system that plays important roles in lipid homeostasis and protection from atherosclerosis. ApoE is characterized by structural plasticity and thermodynamic instability and can undergo significant structural rearrangements as part of its biological function. Mutations in the 136-150 region of the N-terminal domain of apoE, reduce its low density lipoprotein (LDL) receptor binding capacity and have been linked with lipoprotein disorders, such as type III hyperlipoproteinemia (HLP) in humans. However, the LDL-receptor binding defects for these apoE variants do not correlate well with the severity of dyslipidemia, indicating that these variants may carry additional properties that contribute to their pathogenic potential.Methodology/principal findingsIn this study we examined whether three type III HLP predisposing apoE3 variants, namely R136S, R145C and K146E affect the biophysical properties of the protein. Circular dichroism (CD) spectroscopy revealed that these mutations do not significantly alter the secondary structure of the protein. Thermal and chemical unfolding analysis revealed small thermodynamic alterations in each variant compared to wild-type apoE3, as well as effects in the reversibility of the unfolding transition. All variants were able to remodel multillamelar 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) vesicles, but R136S and R145C had reduced kinetics. Dynamic light scattering analysis indicated that the variant R136S exists in a higher-order oligomerization state in solution. Finally, 1-anilinonaphthalene-8-sulfonic acid (ANS) binding suggested that the variant R145C exposes a larger amount of hydrophobic surface to the solvent.Conclusions/significanceOverall, our findings suggest that single amino acid changes in the functionally important region 136-150 of apoE3 can affect the molecule's stability and conformation in solution and may underlie functional consequences. However, the magnitude and the non-concerted nature of these changes, make it unlikely that they constitute a distinct unifying mechanism leading to type III HLP pathogenesis.

Dataset Information

Modern prevalence of dysbetalipoproteinemia (Fredrickson-Levy-Lees type III hyperlipoproteinemia).

Publications

Modern prevalence of dysbetalipoproteinemia (Fredrickson-Levy-Lees type III hyperlipoproteinemia).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets