Paraoxonase 1 gene promoter polymorphisms are associated with the extent of stenosis in coronary arteries

HDL-associated paraoxonase1 (PON1) is believed to be an important anti-oxidative enzyme in the retardation of atherosclerosis. In this study, we determined haplotypes of three SNPs within the PON1 gene promoter to elucidate association of functional sites with coronary artery disease (CAD). We applied a direct haplotyping procedure through ARMS (Amplification Refractory Mutation System) and RFLP (Restriction Fragment Length Polymorphism) analysis techniques. The haplotypes of the G(- 907)C, A(- 162)G and C(- 107)T polymorphisms within the 5' region of the PON1 gene were determined in 99 patients and 66 controls who were evaluated angiographically for the presence and extent of stenosis in coronary arteries. The genotype and haplotype distributions had significant differences between patient subgroups (One-, Two- and Three-vessel disease) but not between the patient and control groups. Multivariate analyses suggested decreased arylesterase activity is the most important independent factor in the CAD severity. The increase of high activity variants [G(- 907) and C(- 107)] within the two-allelic haplotypes was reversely associated with the extent of stenosis in coronary arteries. However, we could not determine the independent involvement each of the C(- 107)T and G(- 907)C polymorphisms on the extent of stenosis. We found no significant association between the A(- 162)G polymorphism and the extent of stenosis in vessels. The study indicated the association of polymorphic variations within the PON1 gene promoter haplotypes with the serum arlyesterase activity. The arlyesterase activity was also associated with the extent of stenosis in coronary arteries but not with primary development of atherosclerosis.