帕金森病和肌萎缩侧索硬化症中的血管生成素变体。
Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis.
机构信息
Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands.
出版信息
Ann Neurol. 2011 Dec;70(6):964-73. doi: 10.1002/ana.22611.
OBJECTIVE
Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD.
METHODS
We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios.
RESULTS
Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10(-6) for ALS and p = 4.3 × 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD.
INTERPRETATION
The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.
目的
多项研究表明，编码血管生成素（ANG）的基因变异在肌萎缩侧索硬化症（ALS）患者中更为常见。有趣的是，少数携带 ANG 变异的 ALS 患者也表现出帕金森病（PD）的迹象。此外，ALS 患者的亲属患 PD 的风险增加，并且 PD 中同时发生运动神经元疾病的患病率高于基于机会发生的预期。因此，我们研究了 ANG 变异是否会导致 ALS 和 PD。
方法
我们回顾了所有关于 ANG 在 ALS 中的研究，并对额外的样本进行了序列实验，这使我们能够分析来自 15 个中心的 6471 名 ALS 患者和 7668 名对照者的数据（来自欧洲的 13 个中心和来自美国的 2 个中心）。我们对来自欧洲的 6 个中心的 3146 名 PD 患者的 DNA 样本进行了测序（来自欧洲的 5 个中心和来自美国的 1 个中心）。使用变量阈值检验进行统计分析，并使用 Mantel-Haenszel 程序估计比值比。
结果
对 17258 个人的序列数据进行分析表明，与对照组相比，ALS 和 PD 患者的 ANG 变异频率明显更高（ALS 患者为 9.3×10（-6），PD 患者为 4.3×10（-5））。与对照组相比，患者中任何 ANG 变异的比值比为 9.2（ALS）和 6.7（PD）。
结论
这项多中心研究的数据表明，PD、ALS 和 ANG 变异之间存在很强的关联。ANG 是 ALS 和 PD 之间的遗传联系。
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