doi: 10.1161/hq1001.097022
© 2001 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Association Between P-Selectin Gene Polymorphisms and Soluble P-Selectin Levels and Their Relation to Coronary Artery Disease
From the Institut National de la Santé et de la Recherche Médicale (INSERM) U525 (S.C.B., C.F., V.N., F.C., L.T.), Paris, France; and the Department of Medicine II (S.B., H.J.R., C.B., J.M.) and Clinical Chemistry (G.H.), Johannes Gutenberg University, Mainz, Germany.
Correspondence to Laurence Tiret, INSERM U525, Faculté de Médecine, 91 Bd de l’Hôpital, 75634 Paris Cedex 13, France. E-mail tiret{at}idf.inserm.fr
Abstract— P-selectin is a cellular adhesion molecule that mediates the interaction of activated endothelial cells or platelets with leukocytes. Increased levels of soluble P-selectin have been reported in various cardiovascular disorders. We measured serum soluble P-selectin levels as well as 3 polymorphisms of the P-selectin gene (C-2123G, A-1969G, and Thr715Pro) in a large cohort of patients with documented coronary artery disease (n=869) and a healthy control group (n=334). The 3 P-selectin polymorphisms were strongly associated with P-selectin levels and altogether explained 7.3% and 18.6% of the P-selectin variability in patients and controls, respectively. Genotype distributions did not significantly differ between patients and controls. P-selectin levels were increased in patients younger than 55 years of age compared with controls (135.2 vs 114.3 ng/mL, P<0.01). On the contrary, patients older than 65 years of age had significantly lower P-selectin levels than did controls (121.5 vs 134.7 ng/mL, P<0.02). In intermediate age groups, P-selectin levels did not significantly differ between the 2 groups. In conclusion, this study revealed a strong association between P-selectin gene polymorphisms and serum P-selectin levels and a complex age-dependent relation between soluble P-selectin levels and coronary artery disease, which suggests that this molecule might have different roles in the atherothrombotic process.
Key Words: coronary artery disease • P-selectin • polymorphisms • genetics
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