Sardo Maria Adriana, Campo Salvatore, Bonaiuto Michele, Bonaiuto Antonio, Saitta Carlo, Trimarchi Giuseppe, Castaldo Maria, Bitto Alessandra, Cinquegrani Maurizio, Saitta Antonino
Department of Internal Medicine, School of Medicine, University of Messina, Azienda Ospedaliera Universitaria, 'G. Martino', Messina, Italy.
Curr Med Res Opin. 2005 May;21(5):777-84. doi: 10.1185/030079905X45170.
Serum paraoxonase (PON1), a high density lipoprotein (HDL)-bound antioxidant enzyme, plays a role in atherosclerosis. An increase in PON1 activity has been reported following statin treatment.
In the present study the following factors were evaluated: the influence of PON1 gene Q192R, L55M and T(-107)C polymorphisms on the response of LDL oxidisability and PON1 activity to atorvastatin treatment.
205 Sicilian subjects with primary hypercholesterolaemia (HCh) and 69 healthy subjects as controls were concurrently enrolled. Hypercholesterolaemic patients were randomly divided into two groups: an atorvastatin group (10 mg/day atorvastatin) and a placebo group. Lipid profile, markers of LDL resistance to in vitro oxidation (lag-phase, oxidation rate and thiobarbituric acid-reactive substances), vitamin E content in LDL, PON1 activity and genotypes in both HCh and control subjects were determined at baseline. The same parameters were measured again after 3 weeks of treatment in both the atorvastatin and placebo groups.
HCh subjects showed significantly lower LDL resistance to oxidation, vitamin E content and PON1 activity levels than controls. A strong association was found among PON1 T(-107)C genotypes, LDL susceptibility to oxidation, vitamin E content and PON1 activity. After treatment, the atorvastatin group displayed a significant decrease in total cholesterol, LDL-cholesterol levels, and LDL susceptibility to oxidation, and an increase in vitamin E content and PON1 activity, compared with baseline values. Unlike PON1 activity levels, no difference among PON1 gene polymorphisms and reduction in markers of LDL oxidisability was observed.
These results show, for the first time, that atorvastatin is able to improve the resistance to LDL oxidation independently of PON1 gene polymorphism.
血清对氧磷酶（PON1）是一种与高密度脂蛋白（HDL）结合的抗氧化酶，在动脉粥样硬化中发挥作用。据报道，他汀类药物治疗后PON1活性会增加。
在本研究中，评估了以下因素：PON1基因Q192R、L55M和T（-107）C多态性对阿托伐他汀治疗后低密度脂蛋白（LDL）氧化易感性和PON1活性反应的影响。
同时纳入205名患有原发性高胆固醇血症（HCh）的西西里受试者和69名健康受试者作为对照。高胆固醇血症患者被随机分为两组：阿托伐他汀组（10毫克/天阿托伐他汀）和安慰剂组。在基线时测定HCh和对照组受试者的血脂谱、LDL体外氧化抗性标志物（滞后期、氧化速率和硫代巴比妥酸反应性物质）、LDL中的维生素E含量、PON1活性和基因型。阿托伐他汀组和安慰剂组在治疗3周后再次测量相同参数。
HCh受试者的LDL氧化抗性、维生素E含量和PON1活性水平显著低于对照组。在PON1 T（-107）C基因型、LDL氧化易感性、维生素E含量和PON1活性之间发现了强烈关联。治疗后，与基线值相比，阿托伐他汀组的总胆固醇、LDL胆固醇水平和LDL氧化易感性显著降低，维生素E含量和PON1活性增加。与PON1活性水平不同，未观察到PON1基因多态性与LDL氧化易感性标志物降低之间的差异。
这些结果首次表明，阿托伐他汀能够独立于PON1基因多态性提高对LDL氧化的抗性。
