Department of Neurology, Laboratory of Neurogenetics, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41100 Larissa, Greece.
B' Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece.
Mol Med Rep. 2022 Apr;25(4). doi: 10.3892/mmr.2022.12662. Epub 2022 Mar 2.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Through a genome‑wide association study (GWAS), the Sec1 family domain‑containing protein 1 (SCFD1) rs10139154 variant at 14q12 has emerged as a risk factor gene for ALS. Moreover, it has been reported to influence the age at onset (AAO) of patients with ALS. The aim of the present study was to assess the association of the SCFD1 rs10139154 polymorphism with the risk of developing ALS. For this purpose, 155 patients with sporadic ALS and 155 healthy controls were genotyped for the SCFD1 rs10139154. The effect of the SCFD1 rs10139154 polymorphism was then examined on the following parameters: i) The risk of developing ALS; ii) the AAO of ALS; iii) the site of ALS onset (patients with bulbar onset ALS vs. healthy controls; and patients with limb onset ALS vs. healthy controls); and iv) the AAO of ALS onset with subgroup analyses based on the site of onset (bulbar and limb, crude and adjusted for sex). The analysis of all the outcomes was performed assuming five genetic models. Crude and adjusted analyses were applied. The threshold for statistical significance was set at 0.05. The results revealed no association between SCFD1 rs10139154 and any of the examined phenotypes in any of the models examined. On the whole, based on the findings of the present study, SCFD1 rs10139154 does not appear to play a determining role in the risk of developing ALS.
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性疾病。通过全基因组关联研究（GWAS），发现 Sec1 家族结构域包含蛋白 1（SCFD1）在 14q12 上的 rs10139154 变体是 ALS 的风险基因。此外，据报道，它还会影响 ALS 患者的发病年龄（AAO）。本研究旨在评估 SCFD1 rs10139154 多态性与发生 ALS 风险之间的关联。为此，对 155 例散发性 ALS 患者和 155 例健康对照者进行了 SCFD1 rs10139154 基因分型。然后检查了 SCFD1 rs10139154 多态性对以下参数的影响：i）发生 ALS 的风险；ii）ALS 的 AAO；iii）ALS 的发病部位（延髓发病 ALS 患者与健康对照组；和肢体发病 ALS 患者与健康对照组）；iv）根据发病部位（延髓和肢体，未调整和调整性别）进行 ALS 发病 AAO 的亚组分析。所有结果的分析均假设了五种遗传模型。进行了粗分析和调整分析。统计显著性的阈值设定为 0.05。结果显示，在任何模型中，SCFD1 rs10139154 与任何检查表型之间均无关联。总体而言，基于本研究的发现，SCFD1 rs10139154 似乎在发展为 ALS 的风险中不起决定性作用。
