Copyright © 2004 by the European Society of Cardiology.
The apolipoprotein E polymorphism is associated with circulating C-reactive protein (the Ludwigshafen risk and cardiovascular health study)
a Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbrugger Platz 15, A-8036 Graz, Austria
b Division of Clinical Chemistry, Department of Medicine, University of Freiburg, Germany
c Division of Endocrinology, Department of Medicine, University Hospital, Ulm, Germany
d Cooperation Unit of Pharmacogenomics and Applied Genome Research, University of Heidelberg, Germany
Received June 29, 2004; revised August 5, 2004; accepted August 12, 2004 * Corresponding author. Tel.: +43 316 385 3145; fax: +43 316 385 3430 (E-mail: winfried.maerz{at}klinikum-graz.at).
BACKGROUND: Statins and cholesterol absorption inhibitors lower the concentration of C-reactive protein (CRP). The genetic polymorphism of apolipoprotein (apo) E is a strong endogenous determinant of sterol homeostasis. We therefore examined the relationship of CRP to the apoE polymorphism.
METHODS AND RESULTS: We studied 739 and 570 subjects with or without stable angiographic coronary artery disease (CAD), respectively. In carriers of apoE2, apoB was lower (P<0.001) than in apoE3/3 homozygotes; in individuals with apoE3/4 and apoE4/4, it was higher (P<0.001). Both in the presence and absence of CAD, CRP was higher in carriers of apoE2 (P=0.002) and apoE3/3 homozygotes (P=0.032) than in individuals with apoE3/4 or apoE4/4. Fibrinogen and white cell count were not related to the apoE genotype. CRP was associated with CAD. Compared to the lowest tertile, crude odds ratios were 1.87 (95% confidence interval (CI), 1.43–2.45, P<0.001) and 2.24 (95% CI, 1.71–2.94, P<0.001) in the second and third tertile. In carriers of apoE2, the use of tertiles defined in controls with apoE2 only diminished the odds ratios for CAD. In apoE3/4 heterozygotes or apoE4/4 homozygotes, the use of tertiles specific for this group only slightly increased the odds ratios.
CONCLUSIONS:: The concentration of CRP, but not fibrinogen nor white blood cells is associated with the apoE polymorphism. The activity of the mevalonate pathway in the liver may be related to the metabolism of CRP. The predictive value of CRP for CAD may be modified by the apoE polymorphism.
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