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Genetic and Mechanistic Insights into the Modulation of Circulating Lipoprotein (a) Concentration by Apolipoprotein E Isoforms

  • Cardiometabolic Disease and Treatment (R. Santos, Section Editor)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Lipoprotein (a) [Lp(a)] is a highly atherogenic lipoprotein species. A unique feature of Lp(a) is the strong genetic determination of its concentration. The LPA gene is responsible for up to 90% of the variance in Lp(a), but other genes also have an impact.

Recent Findings

Genome-wide associations studies indicate that the APOE gene, encoding apolipoprotein E (apoE), is the second most important locus modulating Lp(a) concentrations. Population studies clearly show that carriers of the apoE2 variant (ε2) display reduced Lp(a) levels, the lowest concentrations being observed in ε2/ε2 homozygotes. This genotype can lead predisposed adults to develop dysbetalipoproteinemia, a lipid disorder characterized by sharp elevations in cholesterol and triglycerides. However, dysbetalipoproteinemia does not significantly modulate circulating Lp(a). Mechanistically, apoE appears to impair the production but not the catabolism of Lp(a).

Summary

These observations underline the complexity of Lp(a) metabolism and provide key insights into the pathways governing Lp(a) synthesis and secretion.

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Funding

KC and VB received a scholarship from the European Union (European Regional Development Fund INTERREG V) and the Région Réunion (Saint-Denis, Réunion, France). VB is a recipient of the Canadian Institutes for Health Research (CIHR) fellowship award. GL is supported by the Agence Nationale de la Recherche (Paris, France) Project Grant KRINGLE2 ANR-20-CE14-0009 and by La Fondation De France (FDF-00096274).

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Authors and Affiliations

  1. Laboratoire Inserm, UMR 1188 DéTROI, Université de La Réunion, 2 Rue Maxime Rivière, 97490, Sainte Clotilde, France

    Kévin Chemello, Gilles Lambert & Valentin Blanchard

  2. Division of Lipidology and Cape Heart Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa

    Dirk J. Blom

  3. Division of Chemical Pathology, Department of Pathology, University of Cape Town, Cape Town, South Africa

    A. David Marais

  4. Departments of Medicine, Centre for Heart Lung Innovation, Providence Healthcare Research Institute, St. Paul’s Hospital, University of British Columbia, Vancouver, Canada

    Valentin Blanchard

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  1. Kévin Chemello
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Correspondence to Gilles Lambert.

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Human/Animal Rights and Informed Consents

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

Competing Interests

GL reports research funding and honoraria from Nyrada Inc. GL is a member of the Scientific Advisory board of Nyrada Inc. ADM reports research funding and honoraria from the University of Utrecht. ADM also reports other for the Lipid and Atherosclerosis Society of Southern Africa. KC, VB, and DJB have no relationships to disclose.

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Chemello, K., Blom, D.J., Marais, A.D. et al. Genetic and Mechanistic Insights into the Modulation of Circulating Lipoprotein (a) Concentration by Apolipoprotein E Isoforms. Curr Atheroscler Rep 24, 399–405 (2022). https://doi.org/10.1007/s11883-022-01016-8

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