Association between PON1 rs662 polymorphism and coronary artery disease.

BACKGROUND/

OBJECTIVES

Paraoxonase 1 (PON1) is a plasma enzyme that is capable of inhibiting the progression of atherosclerosis, and is associated with susceptibility of coronary artery disease (CAD). PON protein expression is present in human aortic tissue and it plays an important role in the progression of atherosclerosis. This study aimed to investigate PON1 immunohistochemistry in human coronary arteries, determine its polymorphisms and plasma status, and analyze its association with the risk of CAD.

SUBJECTS/

METHODS

PON1 expression in human coronary artery tissues was detected by immunohistochemical staining. PON1 polymorphisms were determined by polymerase chain reaction direct sequencing in 2456 unrelated Chinese Han individuals. Serum PON1 levels were indirectly reflected by PON1 activity towards paraoxon and phenylacetate by spectrophotometry, and by its concentrations using a human enzyme-linked immunosorbent assay.

RESULTS

Immunohistochemical analysis showed that PON1 expression was lower in atherosclerotic arteries than in normal arteries. PON1 Q192R (rs662) had a significant effect on the risk of CAD (P=0.001). In a logistic regression model, after adjusting for conventional risk factors of CAD, 192R allele carriers had a significantly higher risk of CAD than other allele carriers. Serum PON1 activity and concentrations were significantly reduced in CAD patients compared with controls (P<0.05), and highly associated with the R allele.

CONCLUSIONS

Low PON1 expression in human atherosclerotic coronary arteries is associated with CAD. Moreover, PON1 Q192R polymorphism is significantly associated with susceptibility of CAD in the Chinese Han population, and the 192R allele might be an independent predictor for CAD.