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对氧磷酶 2 C311S 多态性和低水平高密度脂蛋白导致老年急性心肌梗死后死亡率升高。

Paraoxonase2 C311S polymorphism and low levels of HDL contribute to a higher mortality risk after acute myocardial infarction in elderly patients.

机构信息

Immunology Center, Italian National Research Center on Aging (I.N.R.C.A.), Ancona, Italy.

出版信息

Mol Genet Metab. 2009 Nov;98(3):314-8. doi: 10.1016/j.ymgme.2009.05.008. Epub 2009 May 27.

Abstract

It is well known that oxidative stress plays an important role in atherosclerosis and age-related diseases. The antioxidant properties of the Human Paraoxonase gene family (PON1, 2, 3) have been widely investigated, as well as a possible role of the such gene family in cardiovascular disease. In this study, we investigated the relationship between the C311S PON2 polymorphism and the prognosis of acute myocardial infarction (AMI). We analyzed the PON2 C311S polymorphism in 442 elderly patients who had experienced an AMI. PON2 C311S genotypes were identified by PCR based analysis and analyzed as C- (SS genotype) or C+ (CS+CC) carriers. After 1 year of follow-up, the cardiovascular mortality rate in a sub-group of 295 AMI patients was calculated. We found that AMI patients carrying CS+CC genotypes (C+ carriers) had a history of type 2 diabetes mellitus, low levels of HDL-cholesterol and higher levels of TroponinT (TnT). Furthermore, we found that C+ carrier patients with low levels of HDL-cholesterol had an increased risk for mortality after 1 year of follow-up (Log Rank=11.45, p=0.001). Our study suggests a possible role for PON2 C311S polymorphism in the pathogenesis of cardiac ischemic damage. Patients with at least one C allele (C+ carriers) represent a category of subjects at a higher risk for the development of AMI with a worse prognosis. Our findings suggest the need for a more careful clinical monitoring in older persons with such characteristics.

摘要

众所周知,氧化应激在动脉粥样硬化和与年龄相关的疾病中起着重要作用。人类对氧磷酶基因家族(PON1、2、3)的抗氧化特性已经得到了广泛的研究,以及该基因家族在心血管疾病中的可能作用。在这项研究中,我们研究了 C311S PON2 多态性与急性心肌梗死(AMI)预后的关系。我们分析了 442 名经历过 AMI 的老年患者的 PON2 C311S 多态性。通过基于 PCR 的分析确定了 PON2 C311S 基因型,并分析为 C-(SS 基因型)或 C+(CS+CC)携带者。在 295 名 AMI 患者的亚组中进行了 1 年的随访后,计算了心血管死亡率。我们发现携带 CS+CC 基因型(C+携带者)的 AMI 患者有 2 型糖尿病、低水平的高密度脂蛋白胆固醇和高水平的肌钙蛋白 T(TnT)的病史。此外,我们发现低水平的 HDL-胆固醇的 C+携带者在 1 年后的死亡率更高(Log Rank=11.45,p=0.001)。我们的研究表明 PON2 C311S 多态性可能在心脏缺血性损伤的发病机制中起作用。至少携带一个 C 等位基因的患者(C+携带者)代表了一类 AMI 发病风险更高、预后更差的人群。我们的研究结果表明,对于具有这种特征的老年人,需要更仔细的临床监测。

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