Department of Neurology, School of Medicine, University of Campinas-UNICAMP, Campinas, SP, Brazil.
Department of Neurosciences and Behavior Sciences, Ribeirão Preto School of Medicine, University of São Paulo (HCFMRP-USP), Ribeirão Preto, SP, Brazil.
Neurobiol Aging. 2018 Sep;69:292.e15-292.e18. doi: 10.1016/j.neurobiolaging.2018.04.020. Epub 2018 May 8.
Intermediate-length cytosine-adenine-guanine nucleotide repeat expansions in the ATXN2 gene (which encodes for the protein Ataxin-2) have been linked to increased risk for amyotrophic lateral sclerosis (ALS) in different populations. There is no such study in the Brazilian population, which has a mixed ethnic background. We have thus selected 459 patients with ALS (372 Sporadic ALS and 87 Familial ALS) and 468 control subjects from 6 Brazilian centers to investigate this point. We performed polymerase chain reaction to determine the length of the ATXN2 alleles. Polymerase chain reaction products were resolved using capillary electrophoresis on ABI 3500 × l capillary sequencer. We found that ATXN2 intermediate-length expansions (larger than 26 repeats) were associated with an increased risk for ALS (odds ratio = 2.56, 95% confidence interval: 1.29-5.08, p = 0.005). Phenotype in patients with and without ATXN2 expansions was similar. Our findings support the hypothesis that ATXN2 plays an important role in the pathogenesis of ALS also in the Brazilian population.
在不同人群中，ATXN2 基因（编码蛋白 Ataxin-2）中的中等长度胞嘧啶-腺嘌呤-鸟嘌呤核苷酸重复扩展与肌萎缩侧索硬化症 (ALS) 的风险增加有关。巴西人口混合，因此没有这样的研究。我们从 6 个巴西中心选择了 459 名 ALS 患者（372 名散发性 ALS 和 87 名家族性 ALS）和 468 名对照者来调查这一点。我们进行聚合酶链反应以确定 ATXN2 等位基因的长度。聚合酶链反应产物使用 ABI 3500×l 毛细管测序仪上的毛细管电泳进行分离。我们发现 ATXN2 中等长度扩展（大于 26 次重复）与 ALS 的风险增加相关（比值比= 2.56，95%置信区间：1.29-5.08，p = 0.005）。具有和不具有 ATXN2 扩展的患者的表型相似。我们的发现支持 ATXN2 在巴西人群中也在 ALS 的发病机制中起重要作用的假说。
