Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands.
Neurobiol Aging. 2012 Mar;33(3):630.e3-8. doi: 10.1016/j.neurobiolaging.2011.10.029. Epub 2011 Nov 25.
A large genome-wide screen in patients with sporadic amyotrophic lateral sclerosis (ALS) showed that the common variant rs12608932 in gene UNC13A was associated with disease susceptibility. UNC13A regulates the release of neurotransmitters, including glutamate. Genetic risk factors that, in addition, modify survival, provide promising therapeutic targets in ALS, a disease whose etiology remains largely elusive. We examined whether UNC13A was associated with survival of ALS patients in a cohort of 450 sporadic ALS patients and 524 unaffected controls from a population-based study of ALS in The Netherlands. Additionally, survival data were collected from individuals of Dutch, Belgian, or Swedish descent (1767 cases, 1817 controls) who had participated in a previously published genome-wide association study of ALS. We related survival to rs12608932 genotype. In both cohorts, the minor allele of rs12608932 in UNC13A was not only associated with susceptibility but also with shorter survival of ALS patients. Our results further corroborate the role of UNC13A in ALS pathogenesis.
一项针对散发性肌萎缩侧索硬化症（ALS）患者的大型全基因组筛查显示，UNC13A 基因中的常见变异 rs12608932 与疾病易感性相关。UNC13A 调节神经递质的释放，包括谷氨酸。除了改变生存的遗传风险因素外，ALS 的病因在很大程度上仍难以捉摸，为 ALS 提供了有希望的治疗靶点。我们在荷兰基于人群的 ALS 研究中，对 450 名散发性 ALS 患者和 524 名未受影响的对照者的队列中，检查了 UNC13A 是否与 ALS 患者的生存相关。此外，还从参加过之前发表的 ALS 全基因组关联研究的荷兰、比利时或瑞典血统的个体（1767 例病例，1817 例对照）中收集了生存数据。我们将生存与 rs12608932 基因型相关联。在两个队列中，UNC13A 中的 rs12608932 次要等位基因不仅与易感性相关，而且与 ALS 患者的生存时间更短相关。我们的结果进一步证实了 UNC13A 在 ALS 发病机制中的作用。
