Association of anti-oxidized LDL and candidate genes with severity of coronary stenosis in the Women's Ischemia Syndrome Evaluation study.
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.
Department of Human Genetics, and Cardiovascular Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Qi
Q
Chen
Steven E
SE
Reis
Candace
C
Kammerer
Wendy
W
Craig
Dennis M
DM
McNamara
Richard
R
Holubkov
Barry L
BL
Sharaf
George
G
Sopko
Daniel F
DF
Pauly
C Noel Bairey
CN
Merz
M Ilyas
MI
Kamboh
D000906:Antibodies / Q000097:blood*; D015703:Antigens, CD / Q000235:genetics; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics; D001057:Apolipoproteins E / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics; D023921:Coronary Stenosis / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D008071:Lipoprotein Lipase / Q000235:genetics; D008077:Lipoproteins, LDL / Q000276:immunology*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012044:Regression Analysis; D051127:Scavenger Receptors, Class E / Q000235:genetics
C437704:APOA5 protein, human; D000906:Antibodies; D015703:Antigens, CD; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D001057:Apolipoproteins E; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C475476:LRP1 protein, human; D008077:Lipoproteins, LDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; C548261:LPL protein, human; D008071:Lipoprotein Lipase
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