Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan.
Neurogenetics. 2019 May;20(2):65-71. doi: 10.1007/s10048-019-00570-9. Epub 2019 Mar 7.
Intermediate-length CAG repeats in ATXN2 have been widely shown to be a risk factor for sporadic amyotrophic lateral sclerosis (SALS). To evaluate the association of ATXN2 intermediate-length CAG repeat alleles with an increased risk of SALS, we investigated distributions of CAG repeat alleles in 394 patients with SALS and 490 control individuals in the Japanese population. In the intermediate-length repeat units of 29 or more, we identified one SALS patient with 31 repeat units and two control individuals with 30 repeat units. Thus, no significant differences in the carrier frequency of intermediate-length CAG repeat alleles were detected between patients with SALS and control individuals. When we investigated the distribution of "large normal alleles" defined as ATXN2 CAG repeats ranging from 24 up to 33 in the Japanese population compared with those in other populations in previous studies, the frequency of large normal alleles was significantly higher in the European and North American series than in the Japanese series. Moreover, these frequencies in the Turkish, Chinese, Korean, and Brazilian (Latin American) series were also higher than that in the Japanese series. These results raise the possibility that the frequencies of large normal alleles in individual populations underlie the frequencies of ALS risk alleles in the corresponding populations.
在 ATXN2 中存在中等长度的 CAG 重复已被广泛证明是散发性肌萎缩侧索硬化症（SALS）的危险因素。为了评估 ATXN2 中等长度 CAG 重复等位基因与 SALS 风险增加的相关性，我们在日本人群中调查了 394 名 SALS 患者和 490 名对照个体的 CAG 重复等位基因分布。在 29 个或更多的中等长度重复单位中，我们鉴定出一名具有 31 个重复单位的 SALS 患者和两名具有 30 个重复单位的对照个体。因此，在 SALS 患者和对照个体之间未检测到中等长度 CAG 重复等位基因的携带频率存在显著差异。当我们研究在日本人群中定义为 ATXN2 CAG 重复 24 至 33 的“大正常等位基因”的分布与之前研究中其他人群的分布进行比较时，大正常等位基因的频率在欧洲和北美系列中显著高于日本系列。此外，土耳其、中国、韩国和巴西（拉丁美洲）系列中的这些频率也高于日本系列。这些结果提示个体人群中的大正常等位基因频率可能是相应人群中 ALS 风险等位基因频率的基础。
