Polymorphisms of PON1 and PON2 genes in patients with coronary artery disease (Zagreb cohort)

Paraoxonase (PON) is a high density lipoprotein-linked enzyme which exerts its antioxidant effect by removing lipid peroxidation products. Several polymorphic loci have been identified in PON1 (M55L and R192Q) and PON2 (S311C) genes. The aim of our case-control study was to determine whether these genetic variants have an impact on the risk of developing coronary artery disease (CAD). Based on angiography results, the patients were divided into CAD (n=479) and control (n=200) groups. Genotyping was performed by multi-target PCR followed by detection of amplified alleles with linear arrays of immobilized sequence-specific probes on nylon membrane strips. All the genotypes were in Hardy-Weinberg equilibrium. Odds ratios (OR) for the genotypes were calculated by logistic regression after adjusting for age, sex, log (triglyceride), total and HDL-cholesterol, lipoprotein (a), fibrinogen, diabetes, hypertension and smoking. The MM genotype of the PON1 gene was associated with increased risk of developing CAD (OR 1.92, 95% CI 1.12-3.33, p=0.017), whereas the other two polymorphic sites did not show significant association with CAD. Multivariate analysis with age, sex, diabetes, hypertension and smoking as covariates did not show significant effect of any of the three polymorphic loci tested on serum concentrations of total, HDL-, LDL-cholesterol, triglycerides, lipoprotein (a), apolipoproteins AI, B and E. In conclusion, the MM genotype confers significant risk of developing CAD in Croatian population.