Abstract
Atherosclerosis is the major cause of coronary artery disease (CAD), and oxidized LDL (oxLDL) is believed to play a key role in the initiation of the atherosclerotic process. Recent studies show that inflammation and autoimmune reactions are also relevant in atherosclerosis. In this study, we examined the association of antibodies against oxLDL (anti-oxLDL) with the severity of CAD in 558 Women's Ischemia Syndrome Evaluation (WISE) study samples (465 whites; 93 blacks) determined by coronary stenosis (< 20%, 20%-49%, > 50% stenosis). We also examined the relationship of anti-oxLDL with serum lipid levels and nine candidate genes including APOE, APOH, APOA5, LPL, LRP1, HL, CETP, PON1, and OLR1. IgM anti-oxLDL levels were significantly higher in the >20% stenosis group than in the ≥ 20% stenosis group in whites (0.69 ± 0.02 vs. 0.64 ± 0.01, respectively; P = 0.02). IgM anti-oxLDL levels correlated significantly with total cholesterol (r² = 0.01; P = 0.03) and LDL cholesterol (r² = 0.017; P = 0.004) in whites. Multiple regression analysis revealed a suggestive association of LPL/S447X single-nucleotide polymorphism (SNP) with both IgG anti-oxLDL (P = 0.02) and IgM anti-oxLDL (P = 0.07), as well as between IgM anti-oxLDL and the OLR1/3'UTR SNP (P = 0.020). Our data suggest that higher IgM anti-oxLDL levels may provide protection against coronary stenosis and that genetic variation in some candidate genes are determinants of anti-oxLDL levels.
Highlights
Atherosclerosis is the major cause of coronary artery disease (CAD), and oxidized LDL is believed to play a key role in the initiation of the atherosclerotic process
Only cigarette smoking was found to be significantly associated with IgG anti-oxidized LDL (oxLDL) (r2 = 0.044, P = 0.04)
These significant covariates were included in the subsequent general linear regression analysis models to test the association between anti-oxLDL antibody levels and CAD severity, as well as the association between the antibody levels and genotypic variations
Summary
Atherosclerosis is the major cause of coronary artery disease (CAD), and oxidized LDL (oxLDL) is believed to play a key role in the initiation of the atherosclerotic process. We examined the association of antibodies against oxLDL (anti-oxLDL) with the severity of CAD in 558 Women’s Ischemia Syndrome Evaluation (WISE) study samples (465 whites; 93 blacks) determined by coronary stenosis (50% stenosis). IgM anti-oxLDL levels were significantly higher in the >20% stenosis group than in the ʝ20% stenosis group in whites (0.69 ± 0.02 vs 0.64 ± 0.01, respectively; P = 0.02). IgM anti-oxLDL levels correlated significantly with total cholesterol (r2 = 0.01; P = 0.03) and LDL cholesterol (r2 = 0.017; P = 0.004) in whites. Our data suggest that higher IgM anti-oxLDL levels may provide protection against coronary stenosis and that genetic variation in some candidate genes are determinants of anti-oxLDL levels.—Chen, Q., S. Broad Women’s Heart Research Endowment, Cedars-Sinai Medical Center, and the Barbra Streisand Women’s Heart Disease Research and Education Program, Cedars-Sinai Medical Center, Los Angeles, CA
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