Apo E4 and lipoprotein-associated phospholipase A2 synergistically increase cardiovascular risk.
OBJECTIVE
Apolipoprotein E (apoE) has been implicated as conveying increased risk for coronary artery disease (CAD). Previous studies suggest a role of apoE as a modulator of immune response and inflammatory properties. We hypothesized that the presence of apo E4 is associated with an increased inflammatory burden in subjects with CAD as compared to subjects without CAD.


METHODS
ApoE genotypes, systemic (C-reactive protein [CRP], fibrinogen, serum amyloid-A [SAA]) and vascular inflammatory markers (Lipoprotein-associated phospholipase A(2) [Lp-PLA(2)] and pentraxin-3 [PTX-3]) were assessed in 324 Caucasians and 208 African Americans, undergoing coronary angiography.


RESULTS
For both ethnic groups, Lp-PLA(2) index, an integrated measure of Lp-PLA(2) mass and activity, increased significantly and stepwise across apoE isoforms (P = 0.009 and P = 0.026 for African Americans and Caucasians respectively). No differences were found for other inflammatory markers tested (CRP, fibrinogen, SAA and PTX-3). For the top cardiovascular score tertile, apo E4 carriers had a significantly higher level of Lp-PLA(2) index in both ethnic groups (P = 0.027 and P = 0.010, respectively).


CONCLUSIONS
The presence of the apo E4 isoform was associated with a higher level of Lp-PLA(2) index, a marker of vascular inflammation. Our results suggest that genetic variation at the apoE locus may impact cardiovascular disease risk through enhanced vascular inflammation.
Department of Biochemistry, Cerrahpasa Medical School, University of Istanbul, Turkey.
Zeynep
Z
Gungor
Erdembileg
E
Anuurad
Byambaa
B
Enkhmaa
Wei
W
Zhang
Kyoungmi
K
Kim
Lars
L
Berglund
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D001741:Black or African American / Q000235:genetics; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000208:ethnology / Q000235:genetics* / Q000276:immunology*; D003430:Cross-Sectional Studies; D005340:Fibrinogen / Q000032:analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000276:immunology*; D018836:Inflammation Mediators / Q000097:blood*; D010641:Phenotype; D054467:Phospholipases A2 / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D000685:Serum Amyloid A Protein / Q000032:analysis; D000683:Serum Amyloid P-Component / Q000032:analysis; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics; D000099153:Pentraxins
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D053327:Apolipoprotein E4; D015415:Biomarkers; D002097:C-Reactive Protein; D005340:Fibrinogen; D018836:Inflammation Mediators; D054467:Phospholipases A2; D000685:Serum Amyloid A Protein; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C526684:PLA2G7 protein, human