Paraoxonase polymorphism (Gln192Arg) as a determinant of the response of human coronary arteries to serotonin

Background-Oxidation of LDL plays a role in endothelial dysfunction. Paraox onase, an enzyme present on HDL, protects LDL against oxidation. Paraoxonas e activity is genetically determined in part, and 3 genotypes have been des cribed with variable enzymatic activity. We hypothesized that the paraoxona se polymorphism might influence endothelial function. Methods and Results-Twenty-seven patients with clinical manifestations of c oronary artery disease underwent provocative testing by intracoronary admin istration of serotonin. None of the coronary arteries studied had significa nt (>50%) stenosis. Ten patients had the QQ genotype and 17 had the QR geno type. At proximal segments, the mean percentage reduction in lumen diameter in response to serotonin was greater in QQ patients than in QR patients (1 0(-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 Q R 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 endothel ium-derived relaxing factors to counteract the vasoconstrictor effect of se rotonin 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.