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Genetics of HDL-C: a causal link to atherosclerosis?

Julian C van Capelleveen1, Andrea E Bochem, M Mahdi Motazacker

  • 1Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Current Atherosclerosis Reports
|April 18, 2013
PubMed

Insights

High-density lipoprotein cholesterol (HDL-C) levels show an inverse association with cardiovascular disease (CVD) risk. However, genetic studies question if HDL-C

Area of Science:

  • Cardiovascular Science
  • Genetics
  • Epidemiology

Background:

  • Epidemiological studies consistently show an inverse link between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD) risk.
  • Recent intervention trials and Mendelian randomization studies have challenged the causal role of HDL-C in atherosclerosis.
  • HDL-C levels are highly heritable, yet genome-wide association studies (GWAS) explain only a small fraction of this heritability.

Purpose of the Study:

  • To review the association between genetically determined HDL-C levels and atherosclerosis risk.
  • To discuss recent findings on HDL-C-associated genes and GWAS data.
  • To elucidate HDL functionality in relation to CVD risk based on genetic insights.

Main Methods:

  • Review of prospective epidemiological studies.
  • Analysis of large intervention trials and Mendelian randomization studies.
  • Examination of genome-wide association studies (GWAS) data for HDL-C-associated single nucleotide polymorphisms (SNPs).

Main Results:

  • Consistently reported inverse association between HDL-C and CVD risk in epidemiological studies.
  • Questionable causal relationship between HDL-C and atherosclerosis from intervention trials and Mendelian randomization.
  • Limited heritability of HDL-C explained by current GWAS findings.

Conclusions:

  • Genetic studies provide crucial insights into HDL metabolism and functionality.
  • Further research into genetically defined HDL-C levels is needed to clarify its role in atherosclerosis.
  • Understanding HDL functionality is key to elucidating CVD risk.

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