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Evaluation of biochemical algorithms to screen dysbetalipoproteinemia in ε2ε2 and rare APOE variants carriers

  • Louise Michenaud , Nathanaël Marrié , Antoine Rimbert , Oriane Marmontel , Sybil Charrière , Charles Gibert , Caroline Bouveyron , Jade Mammi , Bertrand Cariou , Philippe Moulin and Mathilde Di Filippo ORCID logo EMAIL logo
Published/Copyright: July 29, 2024
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 2

Abstract

Objectives

Dysbetalipoproteinemia (DBL) is a combined dyslipidemia associated with an increased risk of atherosclerotic cardiovascular diseases mostly occurring in ε2ε2 subjects and infrequently in subjects with rare APOE variants. Several algorithms have been proposed to screen DBL. In this work, we compared the diagnostic performances of nine algorithms including a new one.

Methods

Patients were divided into 3 groups according to their APOE genotype: ε2ε2 (“ε2ε2”, n=49), carriers of rare variants (“APOEmut”, n=20) and non-carriers of ε2ε2 nor APOE rare variant (“controls”, n=115). The algorithms compared were those from Fredrickson, Sniderman, Boot, Paquette, De Graaf, Sampson, eSampson, Bea and ours, the “Hospices Civils de Lyon (HCL) algorithm”. Our gold standard was the presence of a ε2ε2 genotype or of a rare variant associated with triglycerides (TG) >1.7 mmol/L. A replication in the UK Biobank and a robustness analysis were performed by considering only subjects with both TG and low-density lipoprotein-cholesterol (LDLc) >90th percentile.

Results

Total cholesterol (TC)/ApoB and NHDLC/ApoB are the best ratios to suspect DBL. In ε2ε2, according to their likelihood ratios (LR), the most clinically efficient algorithms were the HCL, Sniderman and De Graaf’s. In APOEmut, Sniderman’s algorithm exhibited the lowest negative LR (0.07) whereas the HCL’s exhibited the highest positive LR (29). In both cohorts, the HCL algorithm had the best LR.

Conclusions

We proposed a powerful algorithm based on ApoB concentration and the routine lipid profile, which performs remarkably well in detecting ε2ε2 or APOE variant-related DBL. Additional studies are needed to further evaluate algorithms performances in DBL carriers of infrequent APOE variants.

Keywords: algorithms; APOE rare variant; dysbetalipoproteinemia; apolipoprotein B concentration
Corresponding author: Mathilde Di Filippo, PharmD, PhD, Hospices Civils de Lyon, UF Dyslipidémies, Service de Biochimie et de Biologie Moléculaire, Laboratoire de Biologie Médicale MultiSites, Groupement Hospitalier Est, Centre de Biologie et de Pathologies Est (Aile A3), 59 bvd Pinel 69677, Bron Cedex, France; and CarMen Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, France, E-mail:
Louise Michenaud and Nathanaël Marrié contributed equally to this work.

Acknowledgments

We would like to thank physicians and nurses of endocrinology units for recruiting patients, Mrs. Eléonore DIVRY and Sabrina DUMONT for their contribution in determination of LDLc after ultracentrifugation and APOE genotyping, Leonid VELIKOVSKY for his help in AUC determination and comparison using Delong tests. The present research has been conducted using the UK Biobank resource under the application number 49823. We are most grateful to the Bioinformatics Core Facility of Nantes BiRD, member of Biogenouest, Institut Français de Bioinformatique (IFB) (ANR-11-INBS-0013) for the use of its resources and for its technical support.

  1. Research ethics: This study (GENELIP/ASAP study; clinical trial registration number: NCT03939039, https://clinicaltrials.gov/ct2/show/NCT03939039) was authorized by the Hospices Civils de Lyon Institutional Review Board (Scientific and Ethic Committee), approval N°920434 and 21_5588.

  2. Informed consent: Written informed consent was obtained in accordance with the principles of the Declaration of Helsinki and the French bioethic laws.

  3. Author contributions: Clinical assessments: SC, PM. Experiments: conception and design: LM, NM, MDF. Performed the experiments: CB, JM. Analysed the data: LM, NM, AR, OM, SC, CG, BC, PM, MDF. Wrote and reviewed the paper: LM, NM, AR, PM, MDF. Approved the version to be published, agreed to be accountable for all aspects of the work: all authors.

  4. Competing interests: The authors declare that they have no direct or indirect competing interests associated with this publication.

  5. Research funding: None declared.

  6. Data availability: Available on request, respecting ethical laws.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2024-0587).

Received: 2024-05-12
Accepted: 2024-07-16
Published Online: 2024-07-29
Published in Print: 2025-01-29

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2024-0587
Keywords for this article
algorithms; APOE rare variant; dysbetalipoproteinemia; apolipoprotein B concentration

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. CD34+ progenitor cells meet metrology
  4. Reviews
  5. Venous blood collection systems using evacuated tubes: a systematic review focusing on safety, efficacy and economic implications of integrated vs. combined systems
  6. The correlation between serum angiopoietin-2 levels and acute kidney injury (AKI): a meta-analysis
  7. Opinion Papers
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  9. Clostebol and sport: about controversies involving contamination vs. doping offence
  10. Direct-to-consumer testing as consumer initiated testing: compromises to the testing process and opportunities for quality improvement
  11. Perspectives
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  13. Genetics and Molecular Diagnostics
  14. Comparative analysis of BCR::ABL1 p210 mRNA transcript quantification and ratio to ABL1 control gene converted to the International Scale by chip digital PCR and droplet digital PCR for monitoring patients with chronic myeloid leukemia
  15. General Clinical Chemistry and Laboratory Medicine
  16. IVDCheckR – simplifying documentation for laboratory developed tests according to IVDR requirements by introducing a new digital tool
  17. Analytical performance specifications for trace elements in biological fluids derived from six countries federated external quality assessment schemes over 10 years
  18. The effects of drone transportation on routine laboratory, immunohematology, flow cytometry and molecular analyses
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  20. Construction of platelet count-optical method reflex test rules using Micro-RBC#, Macro-RBC%, “PLT clumps?” flag, and “PLT abnormal histogram” flag on the Mindray BC-6800plus hematology analyzer in clinical practice
  21. Evaluation of serum NFL, T-tau, p-tau181, p-tau217, Aβ40 and Aβ42 for the diagnosis of neurodegenerative diseases
  22. An immuno-DOT diagnostic assay for autoimmune nodopathy
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