Centre SLA, CHRU de Tours, Tours, France.
Eur J Hum Genet. 2012 May;20(5):588-91. doi: 10.1038/ejhg.2011.255. Epub 2012 Jan 25.
Abnormal survival motor neuron 1 (SMN1)-copy number has been associated with an increased risk of amyotrophic lateral sclerosis (ALS) in French and Dutch population studies. The aim of this study was to determine whether SMN gene copy number increases the risk of ALS or modulates its phenotype in a cohort of Swedish sporadic ALS (SALS) patients. In all, 502 Swedes with SALS and 502 Swedish controls matched for gender and age were enrolled. SMN1 and SMN2 gene copy numbers were studied by a semi-quantitative PCR method. A genotype-phenotype comparison was performed in order to determine whether SMN genes modulate the phenotype of ALS. The results were also compared with our previously reported French cohort of ALS patients. There was no difference between Swedish patients and controls in the frequency of SMN1 and SMN2 copy numbers. The frequency of SMN1 gene copies differed significantly between the French and Swedish ALS populations. The duration of the disease was significantly longer in the Swedish cohort with homozygous deletions of SMN2 when compared with the French cohort. Abnormal SMN1 gene copy number cannot be considered as a universal genetic susceptibility factor for SALS and this result underlines the importance of reproducing association gene studies in groups from different origins. We also suggest that SMN2 gene copy number might have different effects on ALS progression in disparate human populations.
异常存活运动神经元 1（SMN1）-拷贝数增加与法国和荷兰人群研究中的肌萎缩侧索硬化症（ALS）风险增加相关。本研究的目的是确定 SMN 基因拷贝数是否会增加 ALS 的风险或在瑞典散发型 ALS（SALS）患者队列中调节其表型。共纳入 502 名瑞典 SALS 患者和 502 名性别和年龄匹配的瑞典对照者。通过半定量 PCR 方法研究 SMN1 和 SMN2 基因拷贝数。为了确定 SMN 基因是否调节 ALS 的表型，进行了基因型-表型比较。还将结果与我们之前报道的法国 ALS 患者队列进行了比较。瑞典患者和对照组之间的 SMN1 和 SMN2 拷贝数频率没有差异。SMN1 基因拷贝数在法国和瑞典 ALS 人群之间存在显著差异。与法国队列相比，SMN2 纯合缺失的瑞典队列的疾病持续时间明显更长。异常 SMN1 基因拷贝数不能被视为 SALS 的普遍遗传易感性因素，这一结果强调了在不同来源的人群中重现关联基因研究的重要性。我们还建议 SMN2 基因拷贝数可能对不同人群中 ALS 的进展有不同的影响。
