Abstract 3441: Paraoxonase-192 Polymorphism Interaction with Low HDL Cholesterol in Coronary Artery Risk
Background: Increased lipid peroxidation is associated with accelerated progression of atherosclerosis. Paraoxonase (PON1) is an antioxidative enzyme in high density lipoproteins (HDL), which protects against lipid per oxidation and Coronary Artery Disease (CAD). PON 1 activity is under genetic control and its molecular basis is a polymorphism in the PON 1 gene that shows two common isoforms: Q (192 Gln) with high ability to protect LDL from lipid peroxidation in vitro, and R (Arg) with lower ability. Aim: To explore the interaction of the R allele paraoxonase gene and low HDL cholesterol concentrations, in CAD risk emergence.
Methods: 818 individuals participated in the study, 298 coronary patients, 55.0±10.3 years, 78.9% male sex, and 520 healthy controls, 47.3±12.6 years, 57.5% male sex, age and sex matched. Low HDL-C was defined as <0.90 mmol/L in men and < 1.11 mmol/L in the women. Comparisons of genotypes between cases and control subjects were performed by a chi-square test. Statistical significance was accepted at p<0.05. Odds ratio as well as their 95% confidence intervals for the RR genotypes and HDL deficient subjects were computed using univariate analysis (2x2 tables). To determine the interaction between the RR paraoxonase genotype and HDL-deficient subjects, we used the epidemiologic tables 4x2 and the synergy measures: the additive model (Rothman’s synergy index) and the multiplicative model (Khoury’s synergy index). We calculated the relative excess risk (RERI) and the attributable proportion (AP) due to interaction (Rothman).
Results: The PON 1 RR192 is associated with coronary heart disease [OR=1.61; p=0.043] in whole population. The HDL-deficient subjects 192 RR homozygotes showed an increased risk of CAD (OR=17.38; p< 0.0001) compared to normal HDL 192 RR (OR=1.39; p=0.348) and HDL-deficient subjects not carrying RR genotype (OR=7.79; p<0.0001). The genotype PON 192 RR increases the risk of CAD in the HDL-deficient populations (SI=2.3, SIM=1.6). The attributable proportion due to this interaction (AP) was 0.53, meaning that 53% of CAD was explained by this interaction.
Conclusion: These data suggest the existence of a synergistic effect of the RR 192 PON 1 genotype (with lower ability) and HDL-deficient subjects in CAD emergence.