HDL as a Causal Factor in Atherosclerosis: Insights from Human Genetics

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Liam R Brunham1,2,3

  • 1Department of Medicine, University of British Columbia, Vancouver, Canada. Liam.brunham@ubc.ca.

Current Atherosclerosis Reports
|October 28, 2016
PubMed

Insights

Genetically determined high-density lipoprotein cholesterol (HDL-C) levels may not directly cause reduced atherosclerotic cardiovascular disease (ASCVD) risk. This review examines genetic insights into the complex HDL-C and ASCVD relationship.

Area of Science:

  • Cardiovascular Science
  • Genetics
  • Metabolic Research

Background:

  • High-density lipoprotein cholesterol (HDL-C) is traditionally linked to lower atherosclerotic cardiovascular disease (ASCVD) risk.
  • Recent evidence challenges the direct causal role of HDL-C in preventing atherosclerosis.

Purpose of the Study:

  • To review current knowledge on genetically determined HDL-C levels and ASCVD risk.
  • To explore genetic insights into the causal relationship between HDL and atherosclerosis.

Main Methods:

  • Literature review of genetic studies.
  • Analysis of observational and Mendelian randomization studies.

Main Results:

  • Genetic variations influencing HDL-C levels do not consistently correlate with ASCVD risk reduction.
  • Some genetic factors affecting HDL-C may operate through pathways independent of direct atheroprotection.

Conclusions:

  • The direct causal link between HDL-C levels and ASCVD risk is complex and potentially overstated.
  • Genetic evidence suggests HDL's role in atherosclerosis may be more nuanced than previously assumed.

Keywords:
AtherosclerosisGeneticsHDLLipidsLipoproteins

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