The risk of coronary artery disease in population of Taiwan is associated with Cys-Ser 311 polymorphism of human paraoxonase (PON)-2 gene.

Abstract

Background: Paraoxonase (PON), a high density lipoprotein (HDL)-associated enzyme, is capable of inhibiting low density lipoprotein (LDL) oxidation by destroying the biologically active phospholipids in oxidatively modified LDL. An increased risk of coronary artery disease (CAD) has shown to associate with polymorphisms of PON gene (PON1) in different population. The risk of CAD associated with the other PON1-like gene, designated PON2, which has a similar function and is structurally related to PON1, is least discussed. A population-based case-control study was conducted to investigate the association between CAD and the polymorphisms at two common codons 148 and 311 of PON2 in the population of Taiwan.

Methods: Totally 364 unrelated, angiographically proved CAD-positive patients (338 male and 26 female) and 337 unrelated, CAD-free control subjects (249 male and 88 female) enrolled in this study. Lipids and lipoproteins profile and the association of PON2 genotypes and allele frequencies were analyzed in all study cohorts.

Results: The plasma levels of HDL-cholesterol and apoA-I were significantly lower in patients with CAD than in control subjects (both p = 0.0001). There was no difference in the genotype frequency distribution at codon 148 of PON2 between CAD patients and the controls. However, age-, sex- and diabetes-adjusted odds ratios for individuals with the SS genotype of the codon 311 polymorphism (Cys --> Ser, PON2*C allele --> PON2*S allele) showed a 4.6-fold higher risk of CAD (95% CI = 1.6-15.3, p = 0.006) they ran. Also, in the control subjects, PON2*C allele carriers (CC and CS genotypes) had higher plasma levels of HDL than cases with the SS genotypes (p = 0.035 and p = 0.012, respectively).

Conclusions: Our data implicate that the genotypic variation at codon 311 of PON2 contributes to the susceptibility of CAD in the population of Taiwan.