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Low-density lipoprotein cholesterol and risk of gallstone disease: a Mendelian randomization study and meta-analyses

Stefan Stender1, Ruth Frikke-Schmidt, Marianne Benn

  • 1Department of Clinical Biochemistry, Rigshospitalet, Denmark.

Journal of Hepatology
|August 28, 2012
PubMed

Insights

Elevated low-density lipoprotein cholesterol (LDL-C) does not appear to causally increase the risk of symptomatic gallstone disease. This Mendelian randomization study found no significant genetic link between LDL-C levels and gallstone formation.

Area of Science:

  • Cardiovascular Genetics
  • Gastroenterology
  • Metabolic Diseases

Background:

  • Statins reduce low-density lipoprotein cholesterol (LDL-C) and may offer protection against gallstone disease.
  • The direct causal relationship between plasma LDL-C levels and gallstone disease risk remains uncertain.

Purpose of the Study:

  • To investigate whether elevated plasma LDL-C is a causal risk factor for symptomatic gallstone disease.

Main Methods:

  • A Mendelian randomization approach was employed using genetic data from 63,051 individuals in a Danish prospective cohort study.
  • Eight genetic variants in APOE, APOB, LDLR, and PCSK9 genes known to affect LDL-C were genotyped.
  • Meta-analyses included studies on APOE and APOB genetic variants.

Main Results:

  • Observational analysis showed no increased risk of symptomatic gallstone disease with higher LDL-C quintiles.
  • Individual and combined genetic variants associated with LDL-C levels did not predict symptomatic gallstone disease risk.
  • Meta-analyses of APOE and APOB variants did not reveal a causal association with gallstone disease.

Conclusions:

  • Findings from observational, genetic, and meta-analysis studies suggest that elevated plasma LDL-C is not causally linked to an increased risk of symptomatic gallstone disease.
Abstract

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