Ombres D, Pannitteri G, Montali A, Candeloro A, Seccareccia F, Campagna F, Cantini R, Campa P P, Ricci G, Arca M
Istituto di Terapia Medica Sistematica , II Cattedra di Cardiologia and Istituto di Chirurgia del Cuore e dei Grossi Vasi, Università di Roma "La Sapienza", Italy.
Arterioscler Thromb Vasc Biol. 1998 Oct;18(10):1611-6. doi: 10.1161/01.atv.18.10.1611.
Serum paraoxonase (PON) is an HDL-bound enzyme protecting LDL from oxidation. A common polymorphism of the paraoxonase gene (PON1) involving a Gln-to-Arg interchange at position 192 has been demonstrated to modulate PON activity toward paraoxon, a nonphysiological substrate; Arg192 (allele B) is associated with higher activity than Gln192 (allele A). This polymorphism has been proposed as a genetic marker of risk for coronary artery disease (CAD). However, the relationships between codon 192 PON1 genotypes, coronary atherosclerosis, and the occurrence of myocardial infarction (MI) are still controversial. PON1 genotypes were determined in 472 consecutive subjects (>40 years old) who underwent coronary angiography. CAD (>50% stenosis) was detected in 310 subjects (CAD+); 162 subjects with <10% stenosis served as controls (CAD-). We also evaluated 204 randomly selected individuals as population controls. PON1 genotypes were determined by PCR and AlwI restriction enzyme digestion. Frequencies of alleles A and B were 0. 70 and 0.30 in angiographically assessed subjects and 0.73 and 0.27 in population controls, respectively (chi2=2.0; P<0.3). Distribution of PON1 genotypes in CAD+ were not significantly different from those in CAD- (chi2=2.10; P<0.3). Similarly, no differences were observed in the subgroup of CAD+ with MI nor in that at higher oxidative risk (smokers and/or diabetics). After controlling for other coronary risk factors, no association was found between PON1 alleles and the presence of CAD. PON1 AA genotype was associated with reduced concentration of apolipoprotein B-containing triglyceride-rich lipoproteins. This study did not provide evidence of a significant association between codon 192 PON1 genotypes and coronary atherosclerosis in Italian patients. However, it did confirm that the PON1 low-activity allele is associated with a less atherogenic lipid profile.
血清对氧磷酶（PON）是一种与高密度脂蛋白（HDL）结合的酶，可保护低密度脂蛋白（LDL）不被氧化。已证实对氧磷酶基因（PON1）的一种常见多态性，即第192位的谷氨酰胺（Gln）与精氨酸（Arg）互换，可调节对氧磷酶对对氧磷（一种非生理性底物）的活性；精氨酸192（等位基因B）比谷氨酰胺192（等位基因A）具有更高的活性。这种多态性已被提议作为冠状动脉疾病（CAD）风险的遗传标志物。然而，第192密码子PON1基因型、冠状动脉粥样硬化与心肌梗死（MI）发生之间的关系仍存在争议。对472名接受冠状动脉造影的连续受试者（年龄>40岁）进行了PON1基因型测定。在310名受试者（CAD+）中检测到CAD（狭窄>50%）；162名狭窄<10%的受试者作为对照（CAD-）。我们还评估了204名随机选择的个体作为人群对照。通过聚合酶链反应（PCR）和AlwI限制性内切酶消化来确定PON1基因型。在经血管造影评估的受试者中，等位基因A和B的频率分别为0.70和0.30，在人群对照中分别为0.73和0.27（卡方检验=2.0；P<0.3）。CAD+组中PON1基因型的分布与CAD-组无显著差异（卡方检验=2.10；P<0.3）。同样，在患有MI的CAD+亚组或氧化风险较高（吸烟者和/或糖尿病患者）的亚组中也未观察到差异。在控制了其他冠状动脉危险因素后，未发现PON1等位基因与CAD的存在之间存在关联。PON1 AA基因型与含载脂蛋白B的富含甘油三酯脂蛋白浓度降低有关。本研究未提供证据表明意大利患者中第192密码子PON1基因型与冠状动脉粥样硬化之间存在显著关联。然而，它确实证实了PON1低活性等位基因与动脉粥样硬化性较低的血脂谱相关。
