Paraoxonase 1 gene (Gln192 -Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus
Paraoxonase 1 gene (Gln192 -Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus
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DOI：
10.1016/j.ehj.2012.01.002
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发表时间：
2012-06-01
影响因子：
1.1
通讯作者：
Elnajjar, Mostafa Mohamed
中科院分区：
文献类型：
--
作者：
Elnoamany, Mohamed Fahmy;Dawood, Ashraf Abdelraouf;Elnajjar, Mostafa Mohamed
背景：对氧磷酶1(PON1)被报道具有抗氧化和心脏保护作用。近年来，PON1基因第192位谷氨酰胺(Gln)、精氨酸(Arg)或B型多态与糖尿病(DM)患者的冠状动脉病变(CAD)相关。目的：探讨PON1基因(Gln 192-Arg)多态性与2型糖尿病合并冠心病的发生、程度和严重程度的关系。方法：将180例可疑冠心病患者按是否合并冠心病分为4组：非糖尿病非冠心病组40例，糖尿病非冠心病组45例，糖尿病合并冠心病组47例，糖尿病合并冠心病组48例。结果：Ⅰ、Ⅱ组Gln等位基因(A型)频率明显高于Ⅲ组和Ⅳ组(分别为62.5%、60%和38.3%、31.25%，P<0.05)；0.001)，而Arg等位基因(B型+AB型)在缺血组III和IV组显著高于非缺血组(分别为61.7%，68.75%vs.37.5%，40%，p<；0.001)。冠心病合并糖尿病(IV组)的严重程度评分和血管评分显著高于单纯冠心病(III组)(分别为9.7±2.97，2.44±0.56比6.99+/-3.71，1.67±0.89，p<；0.001)血管评分为3的患者的严重程度评分和Arg等位基因频率显著高于血管评分为2的患者，后者的严重程度评分和Arg等位基因频率也显著高于血管评分为1的患者(8.90±2.79vs.5.21±2.13和80.49%vs.67.86%)、(5.21±2.13vs.3.11+/-0.89和67.86%vs.53.85%)，p<；0.001。在预测冠心病的多因素Logistic回归分析中，年龄[OR2.99，CI(1.11-10.5)，p<；0.01]、吸烟[OR4.13，CI(1.37-11.7)，p<；0.001]、低密度脂蛋白胆固醇100 mg/dL[OR4.31，CI(1.25-12.5)，p<；0.001]、高密度脂蛋白胆固醇和lt；40 mg/dL[OR5.11，CI(1.79~16.33)，p<；0.001]和PON1192Arg等位基因[OR4.62，CI(1.67~13.57)，p<；0.001]是冠心病的独立预测因子。结论：PON1192基因Arg等位基因是冠心病的独立危险因素，不仅与冠心病的存在有关，而且与冠心病的程度和严重程度有关，其影响在糖尿病患者中更为明显。(C)2012年埃及心脏病学会。爱思唯尔B.V.制作和主办。保留所有权利。
Background: Paraoxonase 1 (PON1) is reported to have 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 (Gln 192-Arg) polymorphism 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 four groups: Group I (n = 40 patients) nondiabetic subjects without CAD, Group II (n = 45 patients) diabetic patients without CAD, Group III (n = 47 patients) nondiabetic patients with CAD and Group IV (n = 48 patients) diabetic patients with CAD. PON1(Gln 192-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 and IV) compared to nonischemic groups (I and II) (61.7%, 68.75% vs. 37.5%, 40%, respectively, 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 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. (C) 2012 Egyptian Society of Cardiology. Production and hosting by Elsevier B.V. All rights reserved.