Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Lab of Neurodegenerative Disorders, Institute of Inflammation and Immunology (III), Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
BMC Med. 2022 Jun 27;20(1):209. doi: 10.1186/s12916-022-02411-3.
The time of survival in patients with amyotrophic lateral sclerosis (ALS) varies greatly, and the genetic factors that contribute to the survival of ALS are not well studied. There is a lack of a comprehensive study to elucidate the role of genetic factors in the survival of ALS.
The published studies were systematically searched and obtained from PubMed, EMBASE, and the Cochrane Library without any language restrictions from inception to Oct 27, 2021. A network meta-analysis for ALS causative/risk genes and a systematic review and pairwise meta-analysis for other genetic modifiers were conducted. The PROSPERO registration number: CRD42022311646.
A total of 29,764 potentially relevant references were identified, and 71 papers were eligible for analysis based on pre-decided criteria, including 35 articles in network meta-analysis for 9 ALS causative/risk genes, 17 articles in pairwise meta-analysis for four genetic modifiers, and 19 articles described in the systematic review. Variants in three genes, including ATXN2 (HR: 3.6), C9orf72 (HR: 1.6), and FUS (HR:1.8), were associated with short survival of ALS, but such association was not identified in SOD1, TARDBP, TBK1, NEK1, UBQLN2, and CCNF. In addition, UNC13A rs12608932 CC genotype and ZNF521B rs2275294 C allele also caused a shorter survival of ALS; however, APOE ε4 allele and KIFAP3 rs1541160 did not be found to have any effect on the survival of ALS.
Our study summarized and contrasted evidence for prognostic genetic factors in ALS and would help to understand ALS pathogenesis and guide clinical trials and drug development.
肌萎缩侧索硬化症（ALS）患者的生存时间差异很大，有助于 ALS 生存的遗传因素尚未得到很好的研究。缺乏全面研究来阐明遗传因素在 ALS 生存中的作用。
系统地检索并从 PubMed、EMBASE 和 Cochrane Library 中获取发表的研究，无任何语言限制，检索时间从建库至 2021 年 10 月 27 日。对 ALS 病因/风险基因进行网络荟萃分析，并对其他遗传修饰物进行系统评价和成对荟萃分析。PROSPERO 注册号：CRD42022311646。
共确定了 29764 篇潜在相关参考文献，根据预先确定的标准，有 71 篇论文符合分析条件，包括 35 篇网络荟萃分析 ALS 9 个病因/风险基因的文章、4 个遗传修饰物的 17 篇成对荟萃分析文章和系统综述中描述的 19 篇文章。三个基因的变异，包括 ATXN2（HR：3.6）、C9orf72（HR：1.6）和 FUS（HR：1.8），与 ALS 较短的生存时间相关，但在 SOD1、TARDBP、TBK1、NEK1、UBQLN2 和 CCNF 中未发现这种关联。此外，UNC13A rs12608932 CC 基因型和 ZNF521B rs2275294 C 等位基因也导致 ALS 生存时间缩短；然而，未发现 APOE ε4 等位基因和 KIFAP3 rs1541160 对 ALS 生存有任何影响。
我们的研究总结并对比了 ALS 预后遗传因素的证据，有助于理解 ALS 的发病机制，并指导临床试验和药物开发。
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