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Genetics of remnant cholesterol

Anders B Wulff1,2, Børge G Nordestgaard1,2,3

  • 1Department of Clinical Biochemistry.

Current Opinion in Lipidology
|April 25, 2025
PubMed
Abstract

Insights

Remnant cholesterol, a risk factor for atherosclerotic cardiovascular disease (ASCVD), is influenced by genetic factors. Understanding these genetic determinants, particularly those affecting lipoprotein lipase (LPL), can reveal new therapeutic targets.

Area of Science:

  • Cardiovascular Genetics
  • Lipid Metabolism
  • Pharmacogenomics

Background:

  • Remnant cholesterol is an emerging target for reducing residual atherosclerotic cardiovascular disease (ASCVD) risk in statin-treated patients.
  • Novel therapies like antisense oligonucleotides and monoclonal antibodies enable targeted intervention in pathological pathways.
  • Identifying genetic links to remnant cholesterol can guide the evaluation of drug targets.

Purpose of the Study:

  • To explore genetic determinants of remnant cholesterol.
  • To investigate the relationship between these genetic factors and ASCVD risk.
  • To identify and evaluate potential drug targets for managing remnant cholesterol.

Main Methods:

  • Human genetic epidemiology studies.
  • Analysis of genetic variants influencing lipoprotein metabolism.
  • Investigation of genes affecting lipoprotein lipase (LPL) activity.

Main Results:

  • Several genetic variants impacting remnant cholesterol levels have been identified.
  • Genes such as APOC3, ANGPTL3, and ANGPTL4, which regulate LPL activity, are key determinants.
  • Lipoprotein lipase (LPL) plays a central role in remnant lipoprotein metabolism.

Conclusions:

  • Remnant cholesterol is considered a likely causal factor in ASCVD development.
  • Genetic studies have pinpointed several genes, many related to LPL function, that influence remnant cholesterol.
  • Some identified genes are already therapeutic targets, while others are under investigation for their lipid-lowering effects.
Keywords:
geneticsremnant cholesteroltherapeutic targets

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