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

Abstract

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 (Ͼ50%) 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

The paraoxonase PON1 promoter polymorphism C(-107)T is associated with increased serum glucose concentrations in non-diabetic patients

“…Our study suggests PON1 polymorphisms could reflect, and possibly contribute to abnormal glucose control and hence insulin resistance, a risk factor for these complications. A recent study showed PON1 genotypes (of the Q192R polymorphism) to be associated with endothelial dysfunction in coronary patients [59].…”

Paraoxonase gene polymorphisms and coronary reactivity in young healthy men

“…According to power calculation, 49 subjects were enough to conclude that the difference that we found in blood flow at rest between PON R/Q192 genotypes was also statistically valid. To our knowledge, only one previous study has examined the association between PON R/Q192 polymorphism and coronary vasomotor tone [19]. In that study patients with clinical manifestations of CAD underwent invasive testing by intracoronary administration of serotonin.…”

“…One candidate gene is PON1. To our knowledge, there is only one previous study which has investigared the association between PON R/Q192 polymorphism and coronary vasodilatation [19]. In that study patients underwent coronary angiography, which is an invasive procedure and thus not ethically justified when early changes in the coronary vessels of healthy subjects are studied.…”

Impact of Paraoxonase Polymorphism (Q192R) on Endothelial Function in Intact Coronary Circulation

“…In contrast to previous reports and the present study, Bauters et al reported that the Q allele is associated with a greater degree of serotonin-induced epicardial coronary vasoconstriction in patients with coronary artery disease, suggesting that the Q allele, rather than the R allele, may be a risk factor for coronary heart disease (8). They showed that the biological mechanism by which PON1 polymorphisms influence coronary vasomotion may be unrelated to LDL oxidation (8). Further studies are needed to examine the relationship between PON1 polymorphisms and coronary vasomotion and its mechanism.…”

“…Several studies have suggested that the PON1 Q192R polymorphism is associated with coronary vasomotor tone (8,9).…”