260 PON1-Q192R gene polymorphism and myocardial infarction in tunisian population

Abstract

Paraoxonase (PON1), an enzyme closely associated with high-density lipoproteins, appears to exert an important antioxidant effect by removing lipid peroxidation products. PON1 may also play a role in the pathogenesis of arterial thrombosis and atherosclerosis. The PON1 gene polymorphism involves a Gln → Arg interchange at codon 192 defined by a low-activity isoform (Q allele) and a high-activity isoform (R allele) and has been related in some studies to myocardial infarction (MI). The purpose of the present study was to assess the relationship between PON1-192 polymorphism, and myocardial infarction in Tunisian population. A total of 303 Tunisian patients with MI and 408 healthy controls were included in the study. Diagnosis of MI was confirmed according to the European Society of Cardiology criteria. The PON1-Q192R genotypes were determined by polymerase chain reaction (PCR) amplification and restriction analysis. The genotypes frequencies were in agreement with those predicted by the Hardy-Weinberg equilibrium in MI patients (X 2 =5.52;p=0.63) and controls (X 2 =4.126; p=0.127). A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with MI had a frequency of 17.1% for RR genotype, 41.1% for the QR genotype and 41.7% for the QQ genotype. The controls had a frequency of only 10.9% for the RR genotype, 37.4% for the QR genotype and 51.6% for the RR genotype (X 2 =9.63, p=0.008). The MI patient group showed a significantly higher frequency of R allele compared to controls (37.75% vs. 29.55%; X 2 =10.74; p<0.001). In comparison to the QQ homozygotes, the OR (95%CI) for MI was 1.35 (0.992-1.86) for QR heterozygotes and 1.93 (1.24-3.02) for RR homozygotes. In multivariate analysis, PON1-Q192R polymorphism is associated with MI (p=0.02). The other factors independently associated with MI are age (p<0.001), cigarette smoking (p<0.001), hypertension (p<0.02), diabetes mellitus (p<0.001) and dyslipidemia (p<0.01). Our results show that PON1-192 polymorphism is independently associated with myocardial infarction in our population.