Department of Neurology, Laboratory of Neurodegenerative Disorders, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Neurology, Laboratory of Neurodegenerative Disorders, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Neurobiol Aging. 2021 Jul;103:152.e1-152.e6. doi: 10.1016/j.neurobiolaging.2021.02.022. Epub 2021 Mar 1.
The solute carrier (SLC) transporters have been suggested to play important roles in neurodegenerative disorders. Recently, seven SLC transporters were identified to be associated with Parkinson's disease (PD) by genome-wide association studies. However, few replications were conducted, and whether rare variants in these genes were associated with PD was not explored yet. To elucidate the genetic associations of these SLCs with PD, we investigated the rare variants in 743 Chinese early-onset PD (EOPD) patients using whole-exome sequencing, and evaluated the association between rare variants and PD at allele and gene levels. Totally, 58 rare variants were identified in SLC50A1, SLC41A1, SLC45A3, SLC44A4, SLC56A2, SLC2A13 and SLC38A1. At allele level, 6 variants were nominally associated with PD, namely p.S423G in SLC45A3, p.I551V, p.T435S, p.R323C and p.V101M in SLC2A13, and p.R285Q in SLC41A1. Gene-based burden analysis showed enrichment of rare variants of SLC2A13 in EOPD. Our study systematically analyzed the genetic involvement of SLCs in EOPD, identified SLC2A13 as a risk gene for PD, and broadened the current mutation spectrum of PD.
溶质载体（SLC）转运蛋白被认为在神经退行性疾病中发挥重要作用。最近，通过全基因组关联研究发现了 7 种 SLC 转运蛋白与帕金森病（PD）有关。然而，进行的复制很少，并且这些基因中的罕见变异是否与 PD 相关尚未得到探索。为了阐明这些 SLC 与 PD 的遗传关联，我们使用全外显子组测序研究了 743 例中国早发性 PD（EOPD）患者中的罕见变异，并在等位基因和基因水平上评估了罕见变异与 PD 之间的关联。总共在 SLC50A1、SLC41A1、SLC45A3、SLC44A4、SLC56A2、SLC2A13 和 SLC38A1 中发现了 58 个罕见变异。在等位基因水平上，有 6 个变异与 PD 具有名义相关性，即 SLC45A3 中的 p.S423G、SLC2A13 中的 p.I551V、p.T435S、p.R323C 和 p.V101M 以及 SLC41A1 中的 p.R285Q。基于基因的负担分析显示，EOPD 中 SLC2A13 的罕见变异富集。我们的研究系统地分析了 SLC 在 EOPD 中的遗传参与，确定 SLC2A13 是 PD 的风险基因，并拓宽了当前 PD 的突变谱。
