for the WISE study group. Association of anti-oxidized LDL and candidate genes with severity of coronary stenosis in the WISE study. J. Lipid Res. 2011. 52: 801-807.
Supplementary key words anti-oxLDL antibodies • genetics • low density lipoproteinCoronary artery disease (CAD) is a multifactorial chronic disease caused by atherosclerosis. Although the initiation and progression of atherosclerosis depends largely on genetic factors and life style factors, the underlying cellular and molecular mechanism remains unclear. Accumulating data suggest that oxidized low-density lipoprotein (oxLDL) plays an important role in the development and progression of atherosclerosis ( 1, 2 ). OxLDL, generated by the action of reactive oxygen species, is taken up by macrophages, which develop into foam cells. Autoantibodies against oxLDL (anti-oxLDL) are found in both atherosclerotic lesions and plasma ( 3 ), and thus, the state of oxidative stress might be measured by serum oxLDL antibody levels ( 4 ). The serum levels of anti-oxLDL have been reported to predict the progression of carotid and coronary atherosclerosis ( 5-8 ). Published studies assessing the relationship between anti-oxLDL antibodies 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 infl ammation 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 ʝ 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 ( r 2 = 0.01; P = 0.03) and LDL cholesterol ( r 2 = 0.017; P = 0.004) in whites. Multiple regression analysis revealed a suggestive association of LPL/S447X single-nucleotide polymorphism (SNP) with both IgG antioxLDL ( 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. -Chen, Q., S. E. Reis, C. Kammerer,
This work was supported