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Association of Cys 311 Ser Polymorphism of Paraoxonase-2 Gene with the Risk of Coronary Artery Disease

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Background: Recently another member of the paraoxonase gene family designated paraoxonase-2 has been identified. Paraoxonase-2 has antioxidant properties similar to paraoxonase-1 and paraoxonase-3. However, in contrast to paraoxonase-1 and paraoxonase-3, paraoxonase-2 is not associated with high-density lipoprotein and may only exert its antioxidant function at the cellular level. Methods: We assessed the frequency and genotype distribution of cys 311 ser paraoxonase-2 polymorphism in 300 subjects (>40 years old) with angiographic documentation of coronary artery disease (150 patients with >50% stenosis served as cases and 150 individuals with <20% stenosis served as controls) to determine the possible association between this mutation and susceptibility for coronary artery disease. The paraoxonase-2 genotypes were determined by polymerase chain reaction and DdeI restriction enzyme digestion. Results: The cases (coronary artery disease positive patients) showed significant differences in the distribution of cys 311 ser paraoxonase-2 genotypes as compared with the controls (coronary artery disease negative subjects, P=0.015). The analysis of paraoxonase-2 genotypes distribution showed higher percentage of CC genotype among coronary artery disease positive compared with coronary artery disease negative (P=0.008). After controlling for other risk factors, the cys 311 ser polymorphism had not correlation with age, body mass index, gender, smoking, diabetes, level of high-density lipoprotein, low-density lipoprotein, triglyceride, and total cholesterol. Conclusion: Our data indicate a major effect of the paraoxonase-2 polymorphism on coronary artery disease risk in patients referred to Shariati Hospital in Tehran.

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