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

Abstract

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.

• Authors: Qi Chen, Steven E Reis, Candace Kammerer, Wendy Y Craig, Sue E LaPierre, Erin Luedecking Zimmer, Dennis M McNamara, Daniel F Pauly, Barry Sharaf, Richard Holubkov, C Noel Bairey Merz, George Sopko, Franklin Bontempo, M Ilyas Kamboh
• Journal: Circulation (Circulation) Vol. 107 Issue 25 Pg. 3146-51 (Jul 01 2003) ISSN: 1524-4539 [Electronic] United States
• PMID: 12810610 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• 3' Untranslated Regions (genetics)
• Alleles
• Apolipoproteins E (genetics)
• Autoantibodies (blood)
• Black People (genetics)
• Coronary Angiography
• Coronary Artery Disease (diagnostic imaging, 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)