Objectives Paraoxonase 1 (PON1) is an high-density lipoprotein (HDL)-associated enzyme capable of inhibiting the progression of atherosclerosis, thus preventing the development of coronary artery disease (CAD). The polymorphisms of PON1 gene are known to affect the PON1 concentration and activity, thereby affect the CAD risk. As to its crucial role in preventing of CAD, we determined PON1 polymorphisms and haplotypes, concentration and activity, in addition to the immunohistochemical analysis of PON1 in this population and correlated them with CAD.
Methods A total of 864 controls and 792 patients with CAD confirmed by angiography (≥ 70% stenosis) were recruited in Shenyang Northern Hospital. The concentration of PON1 was measured with Human PON1 Elisa Kit. PON1 activity towards phenylacetate was determined by spectro-photometrically at 270 nm. In addition, genotypes were determined by polymerase chain reaction (PCR). The genotypes and haplotypes were determined by SHEs is and SNPStats softwares respectively. PON1 expression in coronary and carotid arteries were detected by immunohistochemical analysis.
Results Among all studied polymorphisms, only Q192R (rs662) had significant effect on the risk of CAD (Q192R, P < 0.001). In a logistic regression model, after adjustment for the conventional risk factors for CAD, QR and RR genotypes of Q192R had significantly higher CAD risk. Haplotypes Q-L-T-C-G (OR: 0.511, 95% CI : 0.401∼0.651) was also significantly associated with CAD. Both serum PON1 concentration and activity reduced significantly in CAD patients as compared to the controls (P < 0.001). Immunohistochemical analysis showed that during the atherosclerosis of coronary artery, smooth muscle cell staining for PON1 was greatly reduced as compared to the controls, so did in the external carotid artery.
Conclusions The coding Q192R polymorphism and Q-L-T-C-G haplotype are all independently associated with CAD. Serum PON1 concentration and activity were lower in CAD patients than the controls. Additional with the evidence of immunohistochemical analysis, our data add support to the point that PON1 is a strong factor in predicting the risk of CAD.
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