Paraoxonase 1 gene (Gln192-Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus


Background: Paraoxonase 1 (PON1) is reported to have an antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or (type A)/arginine (Arg) or (type B) polymorphism at position 192 of PON1 gene has been suggested with coronary artery disease (CAD) among patients with diabetes mellitus (DM). However, conflicting results have also been reported. Objectives: To investigate the relationship between PON1 gene (Gln192-Arg) poly-morphism and the presence, extent and severity of CAD in type 2 DM. Methods: The study comprised 180 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD and DM into 4 groups; Group I (n = 40 patients) nondiabetic subjects without CAD, Group II (n = 45 patients) diabetic patients without CAD, Group III (n = 47 patients) non diabetic patients with CAD and Group IV (n = 48 patients) diabetic patients with CAD. PON1 (Gln192-Arg) genotype was assessed using polymerase chain reaction (PCR) followed by AlwI digestion. Results: The frequency of Gln allele (Type A) was significantly higher in group I and group II compared to group III and group IV (62.5%, 60% vs 38.3%, 31.25% respectively, p < 0.001) while the frequency of Arg allele (Type B + Type AB) was significantly higher in ischemic groups (III, IV) compared to non ischemic groups (I,II) (61.7%, 68.75% vs 37.5%, 40% respec-tively, p < 0.001). Patients with CAD and DM (group IV) have significantly higher severity score and vessel score than those with CAD only (group III) (9.7 ± 2.97, 2.44 ± 0.56 vs 6.99 ± 3.71, 1.67 ± 0.89 respectively, p < 0.001) Patients with vessel score 3 had significantly higher severity score and higher Arg allele frequency than patients with vessel score 2, the latter group had also significantly higher severity score and Arg allele frequency than patients with vessel score 1 (8.9 ± 2.79 vs 5.21 ± 2.13 and 80.49% vs 67.86%), (5.21 ± 2.13 vs 3.11 ± 0.89 and 67.86% vs 53.85%), p < 0.001 for all. In multivariate logistic regression analysis of different variables for prediction of CAD, age [OR 2.99, CI (1.11 - 10.5), P < 0.01], smoking [OR 4.13, CI (1.37 - 11.7), P < 0.001], low density lipoprotein (LDL) cholesterol > 100 mg/dL [OR 4.31, CI (1.25 - 12.5), P < 0.001], high density lipoprotein (HDL) cholesterol <40 mg/dL [OR 5.11, CI (1.79 - 16.33), P < 0.001] and PON1 192 Arg allele [OR 4.62, CI (1.67 - 13.57), P < 0.001] were significantly independent predictors of CAD. Conclusion: Arg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and it is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients.

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Elnoamany, M. , Dawood, A. , Azmy, R. and Elnajjar, M. (2012) Paraoxonase 1 gene (Gln192-Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus. World Journal of Cardiovascular Diseases, 2, 29-37. doi: 10.4236/wjcd.2012.21006.

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The authors declare no conflicts of interest.


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