Genetic variation in lectin-like oxidized low-density lipoprotein receptor 1 (LOX1) gene and the risk of coronary artery disease

Circulation. 2003 Jul 1;107(25):3146-51. doi: 10.1161/01.CIR.0000074207.85796.36. Epub 2003 Jun 16.


Background: We examined the association of 3 polymorphisms in the lectin-like oxidized LDL receptor-1 (LOX1 or OLR1) gene with coronary artery disease in the Women's Ischemia Syndrome Evaluation (WISE) study population.

Methods and results: The WISE sample comprised 589 white and 122 black women who underwent angiography for suspected ischemia. The sample was divided into 3 groups: <20% stenosis (38.7%), 20% to 49% stenosis (24.9%), and >or=50% stenosis (35.3%). The three LOX1 polymorphisms (intron 4/G-->A, intron 5/T-->G, and 3' UTR/T-->C) were in linkage disequilibrium and thus behaved as a single polymorphism. The frequency of the 3'UTR/T allele was significantly higher in whites than blacks (49% versus 19%; P<0.0001). Among white women, the frequency of the 3'UTR/T allele carriers (TC+TT genotypes) increased gradually from 67.9% to 75.0% and 79.2% in the <20%, 20% to 49%, and >or=50% stenosis groups, respectively (chi2 trend=6.23; P=0.013). Logistic regression analyses indicated that APOE (odds ratio, 1.90; P=0.007) and LOX1 (odds ratio, 1.67; P=0.025) genotypes were independently associated with the risk of disease and that there was no interaction between the two genes. The 3'UTR/T allele carriers also had significantly higher IgG anti-oxLDL levels than individuals carrying the CC genotype (0.94+/-0.20 versus 0.86+/-0.16; P=0.032). Furthermore, our electrophoretic mobility shift assay data show that the 3'UTR polymorphic sequence affects the binding of a putative transcription factor in an allele-specific manner.

Conclusions: Our data suggest that common genetic variation in the LOX1 gene may be associated with the risk of coronary artery disease in white women.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Alleles
  • Apolipoproteins E / genetics
  • Autoantibodies / blood
  • Black People / genetics
  • Coronary Angiography
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / genetics*
  • Electrophoretic Mobility Shift Assay
  • Female
  • Genetic Variation*
  • Heterozygote
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Introns / genetics
  • Linkage Disequilibrium
  • Odds Ratio
  • Polymorphism, Genetic
  • RNA, Messenger / genetics
  • Receptors, LDL / genetics*
  • Receptors, Oxidized LDL
  • Risk Assessment
  • Risk Factors
  • Scavenger Receptors, Class E
  • White People / genetics


  • 3' Untranslated Regions
  • Apolipoproteins E
  • Autoantibodies
  • Immunoglobulin G
  • Immunoglobulin M
  • OLR1 protein, human
  • RNA, Messenger
  • Receptors, LDL
  • Receptors, Oxidized LDL
  • Scavenger Receptors, Class E