SMN2 gene copy number affects the incidence and prognosis of motor neuron diseases in Japan.

IF 2.1 4区 医学 Q3 GENETICS & HEREDITY BMC Medical Genomics Pub Date : 2024-11-06 DOI:10.1186/s12920-024-02026-y
Tomohiko Ishihara, Akihide Koyama, Naoki Atsuta, Mari Tada, Saori Toyoda, Kenta Kashiwagi, Sachiko Hirokawa, Yuya Hatano, Akio Yokoseki, Ryoichi Nakamura, Genki Tohnai, Yuishin Izumi, Ryuji Kaji, Mitsuya Morita, Asako Tamura, Osamu Kano, Masashi Aoki, Satoshi Kuwabara, Akiyoshi Kakita, Gen Sobue, Osamu Onodera
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Abstract

Background: The copy number status (CNS) of the survival motor neuron (SMN) gene may influence the risk and prognosis of amyotrophic lateral sclerosis (ALS) and lower motor neuron diseases (LMND) other than spinal muscular atrophy (SMA). However, previous studies of this association, mainly from Europe, have yielded controversial results, suggesting possible regional differences. Here, we investigated the effect of the SMN gene in Japanese patients with ALS and LMND.

Methods: We examined the SMN copy numbers and clinical histories of 487 Japanese patients with sporadic ALS (281 men; mean age at onset 61.5 years), 50 with adult LMND (50 men; mean age at onset 58.4 years) and 399 Japanese controls (171 men; mean age 62.2 years). Patients with pathogenic mutations in ALS-causing genes were excluded. SMN1 and SMN2 copy numbers were determined using the droplet digital polymerase chain reaction.

Results: The frequency of a copy number of one for the SMN2 gene was higher in patients with ALS (38.0%) than in healthy controls (30.8%) (odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.04-1.82, p < 0.05). The SMN2 copy number affected the survival time of patients with ALS (median time: 0 copies, 34 months; 1 copy, 39 months; 2 copies, 44 months; 3 copies, 54 months; log-rank test, p < 0.05). Cox regression analysis revealed that the SMN2 copy number was associated with increased mortality (hazard ratio = 0.84, 95% CI = 0.72-0.98, p < 0.05). Also, null SMN2 cases were significantly more frequent in the LMND group (12.0%) than in the control group (4.8%) (OR = 2.73, 95% CI = 1.06-6.98, p < 0.05).

Conclusions: Our findings suggest that SMN2 copy number reduction may adversely affect the onset and prognosis of MND, including ALS and LMND, in Japanese.

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SMN2 基因拷贝数影响日本运动神经元疾病的发病率和预后。
背景:存活运动神经元(SMN)基因的拷贝数状态(CNS)可能会影响肌萎缩性脊髓侧索硬化症(ALS)和除脊髓性肌萎缩症(SMA)以外的下运动神经元疾病(LMND)的患病风险和预后。然而,以前主要在欧洲进行的有关这一关联的研究结果存在争议,表明可能存在地区差异。在此,我们调查了日本 ALS 和 LMND 患者中 SMN 基因的影响:我们研究了 487 名日本散发性 ALS 患者(281 名男性;平均发病年龄 61.5 岁)、50 名成人 LMND 患者(50 名男性;平均发病年龄 58.4 岁)和 399 名日本对照组患者(171 名男性;平均发病年龄 62.2 岁)的 SMN 拷贝数和临床病史。排除了ALS致病基因突变的患者。使用液滴数字聚合酶链反应测定SMN1和SMN2的拷贝数:结果:SMN2基因拷贝数为1的ALS患者(38.0%)高于健康对照组(30.8%)(几率比(OR)=1.37,95%置信区间(CI)=1.04-1.82,P 结论:我们的研究结果表明,SMN2基因拷贝数为1的ALS患者(38.0%)高于健康对照组(30.8%):我们的研究结果表明,SMN2拷贝数的减少可能会对日本人MND(包括渐冻人症和低密度脂蛋白性脊髓侧索硬化症)的发病和预后产生不利影响。
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来源期刊
BMC Medical Genomics
BMC Medical Genomics 医学-遗传学
CiteScore
3.90
自引率
0.00%
发文量
243
审稿时长
3.5 months
期刊介绍: BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.
期刊最新文献
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