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

Association between serum paraoxonase (PON1) gene promoter T(-107)C polymorphism, PON1 activity and HDL levels in healthy Sicilian octogenarians
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DOI:
10.1016/j.exger.2004.03.017
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发表时间:
2004-07-01
影响因子:
3.9
通讯作者:
Saitta, A
Saitta, A
中科院分区:
医学2区
文献类型:
--
作者:
Campo, S;Sardo, MA;Saitta, A

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年龄与增强的低密度脂蛋白(LDL)氧化和动脉粥样硬化相关,因此,80岁以上无心血管疾病的受试者提供了研究抗动脉粥样硬化的保护因素的模型。血清对氧磷酶(PON 1)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PON 1启动子T(-107)C和编码区Gln 192 Arg(Q192 R)和Leu 55 Met(L55 M)多态性对西西里岛健康老年人心血管事件抵抗力的贡献。比较了100名老年人和200名成人的PON 1基因型分布、活性分布和生化指标。老年组HDL-C和PON 1活性均显著高于对照组(P <0.001)。PON 1基因型分布分析显示,老年人中(-107)CC基因型比例高于对照组。在两组中,T(-107)C基因型对PON 1活性和HDL-C水平的影响有显著性差异。CC基因型与较高的PON 1活性和高密度脂蛋白水平相比,TT基因型。总之,我们的研究结果提供了一个强有力的证据表明,在健康的西西里岛人老化的特点可能是PON 1(-107)T '风险'等位基因的频率低,并通过有利的基因型,如(-107)CC,影响PON 1活性和HDL-C水平的高频率。(C)2004年爱思唯尔公司All rights reserved.
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. (C) 2004 Elsevier Inc. All rights reserved.