Paraoxonase-1 (PON1) activity, but not PON1(Q192R) phenotype, is a predictor of coronary artery disease in a middle-aged Serbian population

Abstract

Background: Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated serum enzyme that protects lipoproteins from oxidative modifications. Polymorphisms in the gene, including PON1(Q192R), have been studied. However, inconsistencies regarding the above-mentioned polymorphism obscure its association with vascular disease. Methods: Using a two-substrate (paraoxon/diazoxon) activity method, we investigated the frequencies of PON1Q192R phenotypes in 261 middle-aged subjects: 156 patients with angiographically assessed coronary heart disease (CHD) and 105 CHD-free subjects as the control group. The PON1(192) phenotype was predicted from examination of the two-dimensional plot of hydrolysis rates of diazoxon vs. paraoxon and by using the antimode of the histogram of the ratio of diazoxonase/paraoxonase activity. Results: The PON1Q192R phenotype frequencies in 113 patients with occlusion) 50% (coronary artery disease-positive, CAD+ group) vs. control population were as follows: QQ (0.552 vs. 0.510), QR (0.382 vs. 0.408) and RR (0.066 vs. 0.082); chi(2) = 0.414, p = 0.813. We found lower paraoxonase (POase) and diazoxonase (DZOase) activities in the CAD+ patients when compared to the control population. According to logistic regression analysis, POase activity was a better predictor of coronary disease onset compared with DZOase activity measurements and PON1Q192R phenotyping. Conclusions: We conclude that enzyme activity (within a particular phenotypic group) is more important than phenotype alone in predicting susceptibility to coronary artery disease.