Oliveira Simone A, Mansur Antonio P, Ribeiro Cristina C, Ramires José Antonio F, Annichino-Bizzacchi Joyce M
Hematology Center, University of Campinas, São Paulo, Brazil.
Int J Cardiol. 2004 Mar;94(1):73-7. doi: 10.1016/j.ijcard.2003.05.011.
The paraoxonase (PON) gene family contains at least three members: PON1, PON2, and PON3. The enzyme PON1 has been implicated in the pathogenesis of atherosclerosis. Recently, an association between PON2 and quantitative metabolic phenotypes, such as plasma lipoproteins, plasma glucose, and coronary artery disease (CAD), has been reported. We analyzed two common polymorphisms in PON1 (i.e., M/L55 and R/Q 192 mutations) and PON2 (i.e., G/A148 and C/S311 mutations) in 352 high-risk patients with angiographically defined CAD. These results were compared to those in 380 age- and sex-matched control subjects at high risk for CAD. Polymerase chain reaction with specific primers followed by Hsp92, Alw1, DdeI and Fnu4HI restriction digestion were employed to identify the PON1 M/L55 and R/Q192 and the PON2 G/A148 and C/S311 genotypes, respectively. Univariate analysis showed a higher prevalence of the MM genotype (12% vs. 5%; p=0.004) for the PON1 M/L55 polymorphism and the GG genotype (21% vs. 15%; p=0.047) PON2 G/A148 polymorphism in the control subjects. The PON1 M/L55 mutation (MM genotype) was associated with lower triglyceride levels and the PON2 G/A148 mutation (GG genotype), with higher total and low-density lipoprotein (LDL)-cholesterol levels. No mutation was associated with the number of major coronary artery vessels with a >50% reduction in lumen diameter. Multiple regression analysis disclosed smoking, a family history of CAD, high-density lipoprotein (HDL)-cholesterol and the PON1 M/L55 mutation [OR=0.59 (CI95%: 0.42-0.82); p=0.002] as independent markers for CAD. In contrast to traditional coronary risk factors, the PON1 M/L mutation can be considered predictive of protection against CAD.
对氧磷酶（PON）基因家族至少包含三个成员：PON1、PON2和PON3。PON1酶与动脉粥样硬化的发病机制有关。最近，有报道称PON2与血浆脂蛋白、血糖和冠状动脉疾病（CAD）等定量代谢表型之间存在关联。我们分析了352例经血管造影确诊为CAD的高危患者中PON1的两种常见多态性（即M/L55和R/Q 192突变）以及PON2的两种常见多态性（即G/A148和C/S311突变）。将这些结果与380名年龄和性别匹配的CAD高危对照受试者的结果进行比较。采用特异性引物进行聚合酶链反应，随后进行Hsp92、Alw1、DdeI和Fnu4HI限制性消化，分别鉴定PON1的M/L55和R/Q192以及PON2的G/A148和C/S311基因型。单因素分析显示，对照受试者中PON1 M/L55多态性的MM基因型患病率较高（12%对5%；p=0.004），PON2 G/A148多态性的GG基因型患病率较高（21%对15%；p=0.047）。PON1 M/L55突变（MM基因型）与较低的甘油三酯水平相关，PON2 G/A148突变（GG基因型）与较高的总胆固醇和低密度脂蛋白（LDL）胆固醇水平相关。没有突变与管腔直径减少>50%的主要冠状动脉血管数量相关。多因素回归分析显示，吸烟、CAD家族史、高密度脂蛋白（HDL）胆固醇和PON1 M/L55突变[比值比=0.59（95%可信区间：0.42-0.82）；p=0.002]是CAD的独立标志物。与传统的冠状动脉危险因素相比，PON1 M/L突变可被视为预防CAD的预测指标。
