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Therapeutic Targets of Triglyceride Metabolism as Informed by Human Genetics

Robert C Bauer1, Sumeet A Khetarpal1, Nicholas J Hand1

  • 1Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA 19104-5159, USA.

Trends in Molecular Medicine
|March 19, 2016
PubMed

Insights

Human genetics research reveals triglyceride-rich lipoproteins (TRLs) as a key cause of coronary artery disease (CAD). Targeting lipoprotein lipase (LPL) and hepatic lipogenesis pathways offers new therapeutic strategies for CAD.

Area of Science:

  • Human Genetics
  • Cardiovascular Disease Research
  • Lipid Metabolism

Background:

  • Coronary artery disease (CAD) remains a significant health burden despite advances in hyperlipidemia treatments.
  • Current therapies, including PCSK9 inhibitors, have improved LDL cholesterol management but not fully addressed CAD.
  • Emerging evidence links triglyceride-rich lipoproteins (TRLs) as a causal factor in CAD pathogenesis.

Purpose of the Study:

  • To explore the role of human genetics in identifying novel therapeutic targets for CAD.
  • To investigate the causal relationship between TRLs and CAD risk.
  • To highlight the potential of targeting specific lipid metabolism pathways for CAD intervention.

Main Methods:

  • Review of unbiased human genetics studies, including genome-wide association studies (GWAS).
  • Analysis of whole-genome and whole-exome sequencing data.
  • Examination of epidemiological data linking TRLs to CAD.

Main Results:

  • Human genetics studies identified lipoprotein lipase (LPL) as a key regulator of circulating TRLs.
  • Hepatic lipogenesis pathways were also implicated in TRL regulation.
  • Findings reinforce the causal link between elevated TRLs and increased CAD risk.

Conclusions:

  • Targeting LPL and hepatic lipogenesis pathways presents a promising therapeutic avenue for CAD.
  • Human genetics provides critical insights into novel strategies for managing CAD.
  • Further research into TRLs may lead to much-needed interventions for cardiovascular disease.
Keywords:
GWASgeneticslipogenesistriglycerides

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