Genome-wide association study pinpoints a new functional apolipoprotein B variant influencing oxidized low-density lipoprotein levels but not cardiovascular events: AtheroRemo Consortium

Circ Cardiovasc Genet. 2013 Feb;6(1):73-81. doi: 10.1161/CIRCGENETICS.112.964965. Epub 2012 Dec 17.


Background: Oxidized low-density lipoprotein may be a key factor in the development of atherosclerosis. We performed a genome-wide association study on oxidized low-density lipoprotein and tested the impact of associated single-nucleotide polymorphisms (SNPs) on the risk factors of atherosclerosis and cardiovascular events.

Methods and results: A discovery genome-wide association study was performed on a population of young healthy white individuals (N=2080), and the SNPs associated with a P<5×10(-8) were replicated in 2 independent samples (A: N=2912; B: N=1326). Associations with cardiovascular endpoints were also assessed with 2 additional clinical cohorts (C: N=1118; and D: N=808). We found 328 SNPs associated with oxidized low-density lipoprotein. The genetic variant rs676210 (Pro2739Leu) in apolipoprotein B was the proxy SNP behind all associations (P=4.3×10(-136), effect size=13.2 U/L per allele). This association was replicated in the 2 independent samples (A and B, P=2.5×10(-47) and 1.1×10(-11), effect sizes=10.3 U/L and 7.8 U/L, respectively). In the meta-analyses of cohorts A, C, and D (excluding cohort B without angiographic data), the top SNP did not associate significantly with the age of onset of angiographically verified coronary artery disease (hazard ratio=1.00 [0.94-1.06] per allele), 3-vessel coronary artery disease (hazard ratio=1.03 [0.94-1.13]), or myocardial infarction (hazard ratio=1.04 [0.96-1.12]).

Conclusions: This novel genetic marker is an important factor regulating oxidized low-density lipoprotein levels but not a major genetic factor for the studied cardiovascular endpoints.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apolipoproteins B / genetics*
  • Apolipoproteins B / metabolism*
  • Atherosclerosis / blood
  • Atherosclerosis / genetics
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / genetics*
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome-Wide Association Study*
  • Humans
  • Lipoproteins, LDL / blood*
  • Male
  • Middle Aged
  • Mutation, Missense
  • Polymorphism, Single Nucleotide


  • Apolipoproteins B
  • Lipoproteins, LDL
  • oxidized low density lipoprotein