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评估骨保护素基因、TNFRSF11B 多态性对血清骨保护素水平和颈动脉斑块易损性的遗传影响。

Assessment of the genetic effects of polymorphisms in the osteoprotegerin gene, TNFRSF11B, on serum osteoprotegerin levels and carotid plaque vulnerability.

机构信息

Vascular Medicine and Atherothrombosis Laboratory, Department of Experimental Medicine, Sapienza University of Rome, Polo Pontino, Italy.

出版信息

Stroke. 2011 Nov;42(11):3022-8. doi: 10.1161/STROKEAHA.111.619288. Epub 2011 Sep 8.

DOI:10.1161/STROKEAHA.111.619288

PMID:21903966

Abstract

BACKGROUND AND PURPOSE

Osteoprotegerin (OPG) is a secretory glycoprotein which belongs to the tumor necrosis factor receptor family. Various mechanisms have been suggested by which calcification might alter atherosclerotic plaque stability, but the significance of this intimal calcification is controversial. High concentrations of OPG have been associated with the presence of vascular and cardiovascular diseases. This study was designed to assess the association between gene polymorphisms of the OPG gene (TNFRSF11B), the serum OPG level, and plaque stability in patients with carotid atherosclerosis.

METHODS

We studied 177 patients with internal carotid artery stenosis who underwent carotid endarterectomy and also 303 controls. Carotid endarterectomy samples removed from patients were assessed by immunohistochemistry. Concentrations of OPG were measured and gene polymorphisms were examined by polymerase chain reaction and restriction enzyme analysis and were compared, initially between patients with carotid atherosclerosis and controls, and subsequently between stable and unstable carotid plaques.

RESULTS

We found that the GG genotype of the T245G polymorphism, the CC genotype of the T950C polymorphism, and the CC genotype of the G1181C polymorphism were significantly higher in patients with carotid plaque than in controls (21.5% versus 10.9% , P<0.01; 15.8% versus 7.6%, P<0.01; and 20.3% versus 10.9%, P<0.01, respectively) and that these polymorphisms were associated with high serum OPG levels (4.02 [3.07] versus 2.94 [1.81] pmol/L; P<0.01), which were significantly higher in patients with unstable atherosclerotic plaques (5.86 [4.02] versus 3.53 [1.87] pmol/L; P<0.01).

CONCLUSIONS

The TNFRSF11B gene polymorphisms studied are associated with high serum OPG levels and might be potential markers for plaque instability.

摘要

背景与目的

骨保护素（OPG）是一种分泌型糖蛋白，属于肿瘤坏死因子受体家族。已有多种机制被提出，认为钙化可能改变动脉粥样硬化斑块的稳定性，但这种内膜钙化的意义仍存在争议。OPG 浓度升高与血管和心血管疾病的存在相关。本研究旨在评估骨保护素（OPG）基因（TNFRSF11B）基因多态性、血清 OPG 水平与颈动脉粥样硬化患者斑块稳定性之间的关系。

方法

我们研究了 177 例接受颈动脉内膜切除术的颈内动脉狭窄患者，以及 303 例对照组。对患者颈动脉内膜切除术样本进行免疫组织化学评估。测量 OPG 浓度，并通过聚合酶链反应和限制性内切酶分析检测基因多态性，首先在颈动脉粥样硬化患者与对照组之间进行比较，然后在稳定和不稳定颈动脉斑块之间进行比较。

结果

我们发现，与对照组相比，颈动脉斑块患者的 T245G 多态性 GG 基因型、T950C 多态性 CC 基因型和 G1181C 多态性 CC 基因型明显更高（21.5%比 10.9%，P<0.01；15.8%比 7.6%，P<0.01；20.3%比 10.9%，P<0.01），这些多态性与高血清 OPG 水平相关（4.02[3.07]比 2.94[1.81]pmol/L；P<0.01），不稳定粥样硬化斑块患者的血清 OPG 水平显著更高（5.86[4.02]比 3.53[1.87]pmol/L；P<0.01）。