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(Circulation. 2000;101:740.)
© 2000 American Heart Association, Inc.

Brief Rapid Communication

Paraoxonase Polymorphism (Gln192Arg) as a Determinant of the Response of Human Coronary Arteries to Serotonin

Christophe Bauters, MD; Carole Amant, PhD; Agnès Boulier, PhD; Philippe Cabrol, MD; Eugène McFadden, MRCPI; Patrick Duriez, PhD; Michel E. Bertrand, MD; Philippe Amouyel, MD, PhD

From University and CHRU de Lille (C.B., P.C., E.M., M.E.B., P.A.); INSERM U508, Institut Pasteur de Lille (C.B., C.A., P.A.); and INSERM U325, Institut Pasteur de Lille (A.B., P.D.), Lille, France.

Correspondence to Philippe Amouyel, INSERM U-508, Institut Pasteur de Lille, 1 rue Calmette, 59019 Lille Cedex, France. E-mail philippe.amouyel{at}pasteur-lille.fr

Background—Oxidation of LDL plays a role in endothelial dysfunction. Paraoxonase, an enzyme present on HDL, protects LDL against oxidation. Paraoxonase activity is genetically determined in part, and 3 genotypes have been described with variable enzymatic activity. We hypothesized that the paraoxonase polymorphism might influence endothelial function.

Methods and Results—Twenty-seven patients with clinical manifestations of coronary artery disease underwent provocative testing by intracoronary administration of serotonin. None of the coronary arteries studied had significant (>50%) stenosis. Ten patients had the QQ genotype and 17 had the QR genotype. At proximal segments, the mean percentage reduction in lumen diameter in response to serotonin was greater in QQ patients than in QR patients (10^-5 mol/L: P<0.05; 10^-4 mol/L: P<0.006). Similarly, at distal segments, constriction in response to serotonin was greater in QQ patients than in QR patients (10^-6 mol/L: P<0.03; 10^-5 mol/L: P<0.07).

Conclusions—These results suggest a higher synthesis or release of endothelium-derived relaxing factors to counteract the vasoconstrictor effect of serotonin in patients with the R allele. These findings provide evidence that the paraoxonase polymorphism may play a role in the regulation of coronary vasomotor tone.

Key Words: arteries • coronary disease • vasoconstriction • endothelium

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