Association of Paraoxonase-1 Genotype and Phenotype with Angiogram Positive Coronary Artery Disease

Abstract

Background: It has been shown that increased serum PON1 levels are protective against several disorders. Several single nucleotide polymorphisms (SNPs) of the PON1 gene have been reported to be associated with serum enzyme protein levels and activity. Objective: To investigate the association of SNPs of PON1 and serum paraoxonase activity with coronary artery disease (CAD). Methods: A total of 601 unrelated patients who underwent coronary angiography including those who had 50 stenosis (N=266) and those with <30 stenosis (N=335) were studied. The Paraoxonase gene rs662 and rs840560 SNPs were determined using the ARMS-PCR method and the rs705379 SNP was genotyped using PCR-RFLP analysis. Serum paraoxonase activity was measured using paraoxon as a substrate. A p value of p<0.05 was considered as significant. Results: Serum paraoxonase activity was not significantly different between the study groups. After adjustment for age, sex, hypertension, diabetes mellitus and dyslipidemia, the GG genotype and co-dominant model of rs662 was positively associated with a positive angiogram (respectively, OR=2.424, 95CI 1.123-5.233, p<0.05, OR=1.663, 95%CI 1.086-2.547). Serum paraoxonase activity was significantly higher in the G allele and GG variant of rs662, A allele and AA variant of rs854560 and C allele and CC variant of rs705379. The haplotype analysis has shown that the ATC haplotype was significantly more prevalent among the angiogram negative group. The analysis between groups indicated that the A allele of rs662 was significantly associated with lower paraoxonase activity in the positive angiogram group (p=0.019). Conclusions: The presence of the G allele of the rs662 single nucleotide polymorphism is independently associated to increased risk of CAD.