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西西里岛健康八旬老人血清对氧磷酶(PON1)基因启动子T(-107)C多态性、PON1活性与高密度脂蛋白水平之间的关联

Association between serum paraoxonase (PON1) gene promoter T(-107)C polymorphism, PON1 activity and HDL levels in healthy Sicilian octogenarians.

作者信息

Campo Salvatore, Sardo Maria A, Trimarchi Giuseppe, Bonaiuto Michele, Fontana Luisa, Castaldo Maria, Bonaiuto Antonio, Saitta Carlo, Bitto Alessandra, Manduca Bruno, Riggio Stefania, Saitta Antonino

机构信息

Department of Internal Medicine, 82 Via Camiciotti, 98123, University of Messina, Italy.

出版信息

Exp Gerontol. 2004 Jul;39(7):1089-94. doi: 10.1016/j.exger.2004.03.017.

Abstract

Age is associated with an enhanced low density lipoprotein (LDL) oxidation and atherosclerosis, thus, subjects over 80 years without cardiovascular disease provide a model to investigate the protective factors against atherosclerosis. Serum paraoxonase (PON1), an high density lipoprotein (HDL)-bound enzyme, prevents LDL oxidation. The aim of the present study was to evaluate the contribution of the PON1 promoter T(-107)C and coding region Gln192Arg (Q192R) and Leu55Met (L55M) polymorphisms to the resistance to develop cardiovascular events in Sicilian healthy octogenarians. Distribution of PON1 genotypes and activity, and biochemical parameters, were compared between 100 octogenarians and 200 adults. Individuals in the elderly group displayed significant higher levels of HDL-C (P < 0.001) and PON1 activity (P < 0.001). The analysis of PON1 genotypes distribution showed an higher percentage of (-107)CC among octogenarians compared with controls. A significant difference among T(-107)C genotypes respect to PON1 activity and HDL-C levels occurred in both groups. The CC genotype was associated with higher PON1 activity and HDL levels compared to the TT genotypes. In conclusion, our results provide a strong evidence that in healthy Sicilians ageing may be characterized by a low frequency of PON1 (-107)T 'risk' allele and by an high frequency of favourable genotypes such as (-107)CC, influencing PON1 activity and HDL-C levels.

摘要

年龄与低密度脂蛋白(LDL)氧化增强及动脉粥样硬化相关,因此,80岁以上无心血管疾病的受试者为研究抗动脉粥样硬化保护因素提供了一个模型。血清对氧磷酶(PON1)是一种与高密度脂蛋白(HDL)结合的酶,可防止LDL氧化。本研究的目的是评估PON1启动子T(-107)C以及编码区Gln192Arg(Q192R)和Leu55Met(L55M)多态性对西西里健康百岁老人发生心血管事件抵抗力的影响。比较了100名百岁老人和200名成年人的PON1基因型分布、活性及生化参数。老年组个体的HDL-C水平(P < 0.001)和PON1活性(P < 0.001)显著更高。PON1基因型分布分析显示,与对照组相比,百岁老人中(-107)CC的比例更高。两组中T(-107)C基因型在PON1活性和HDL-C水平方面均存在显著差异。与TT基因型相比,CC基因型与更高的PON1活性和HDL水平相关。总之,我们的结果提供了有力证据,表明在健康的西西里人中,衰老可能表现为PON1(-107)T“风险”等位基因频率较低,以及(-107)CC等有利基因型频率较高,这影响了PON1活性和HDL-C水平。

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