Cao H, Girard-Globa A, Serusclat A, Bernard S, Bondon P, Picard S, Berthezene F, Moulin P
Laboratoire de Métabolisme des Lipides, Université Lyon 1, Hôpital de l'Antiquaille, France.
Atherosclerosis. 1998 Jun;138(2):361-6. doi: 10.1016/s0021-9150(98)00031-8.
Paraoxonase (PON) is an HDL-bound enzyme capable of hydrolyzing lipid peroxides and believed to be in part responsible for the protective effect of HDL against LDL oxidation. Its activity is mainly determined by a gene polymorphism of the PON 1 gene (Glu-Arg 192). Low activity has been related to an elevated incidence of myocardial infarction. In several case-control studies, however, the high activity B allele is paradoxically more prevalent in patients. We have re-investigated this relationship, using carotid intima-media thickness (IMT) as a surrogate continuous variable for macroangiopathy. Genotypes were determined in 197 non insulin-dependent diabetic patients (HbAlc 8.8+/-0.15%, BMI 28.3+/-0.36). IMT, measured by high resolution mode B ultrasound, was the same for all genotypes (AA: 0.83+/-.013, AB 0.82+/-.017 and BB: 0.81+/-.034 mm). Bearers of the B allele displayed higher Lp(a) concentration (AA: 197+/-28, AB: 221+/-26, BB: 225+/-45 mg/l, P=0.024) with a significant linear trend (P < 0.005). Multiple regression showed age and systolic blood pressure, but not Lp(a), to be the main determinants of IMT variability without the contribution of the PON genotype. No consistent differences could be found between genotypes in the peroxidizability of LDL (lag-time, rate of diene production and maximal concentration). Our data support the view that there is no association between the early changes of atherosclerosis as defined by carotid IMT and variation in codon 192 of PON 1.
对氧磷酶（PON）是一种与高密度脂蛋白（HDL）结合的酶，能够水解脂质过氧化物，并且被认为在一定程度上对HDL抵抗低密度脂蛋白（LDL）氧化的保护作用负责。其活性主要由PON 1基因的一个基因多态性（Glu-Arg 192）决定。低活性与心肌梗死发病率升高有关。然而，在一些病例对照研究中，矛盾的是，高活性的B等位基因在患者中更为普遍。我们使用颈动脉内膜中层厚度（IMT）作为大血管病变的替代连续变量，重新研究了这种关系。对197例非胰岛素依赖型糖尿病患者（糖化血红蛋白[HbAlc] 8.8±0.15%，体重指数[BMI] 28.3±0.36）进行了基因分型。通过高分辨率B型超声测量的IMT在所有基因型中相同（AA：0.83±0.013，AB：0.82±0.017，BB：0.81±0.034毫米）。携带B等位基因者的脂蛋白（a）[Lp(a)]浓度更高（AA：197±28，AB：221±26，BB：225±45毫克/升，P = 0.024），且有显著的线性趋势（P < 0.005）。多元回归显示年龄和收缩压是IMT变异性的主要决定因素，而非Lp(a)，且PON基因型无贡献。在LDL的过氧化能力（延迟时间、二烯生成速率和最大浓度）方面，各基因型之间未发现一致差异。我们的数据支持这样一种观点，即由颈动脉IMT定义的动脉粥样硬化早期变化与PON 1第192密码子的变异之间不存在关联。
