Paraoxonase-1 (PON1) activity, but not PON1(Q192R) phenotype, is a predictor of coronary artery disease in a middle-aged Serbian population.
BACKGROUND
Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated serum enzyme that protects lipoproteins from oxidative modifications. Polymorphisms in the gene, including PON1Q192R, 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); chi2=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.
Kotur-Stevuljevic
Jelena
J
Institute for Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia. jkotur@pharmacy.bg.ac.yu
Spasic
Slavica
S
Stefanovic
Aleksandra
A
Zeljkovic
Aleksandra
A
Bogavac-Stanojevic
Natasa
N
Kalimanovska-Ostric
Dimitra
D
Spasojevic-Kalimanovska
Vesna
V
Jelic-Ivanovic
Zorana
Z
D043303:Aryldialkylphosphatase / Q000097:blood* / Q000235:genetics*; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D015022:Yugoslavia / Q000453:epidemiology
D043303:Aryldialkylphosphatase; C468406:PON1 protein, human