Baiyuan Yang1, Haixia Jiang2, Fang Wang3, Shimei Li4, Chongmin Wu3, Jianjian Bao3, Yongyun Zhu3, Zhong Xu3, Bin Liu3, Hui Ren3, Xinglong Yang5. 1. Department of Neurology, Seventh People's Hospital of Chengdu, Chengdu, 690041, Sichuan Province, People's Republic of China. 2. Department of Anesthesia, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan Province, People's Republic of China. 3. Department of Geriatric Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan Province, People's Republic of China. 4. Department of Anesthesia, Kunming Xishan District People's Hospital, Kunming, 650100, Yunnan Province, People's Republic of China. 5. Department of Geriatric Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan Province, People's Republic of China. yxldoc11@163.com.
Abstract
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with both genetic and environmental risk factors. Previous studies trying to find an association between ALS and unc-13 homolog A (UNC13A) gene variants have shown inconsistent results. This study aimed to conduct a meta-analysis of the association between the C allele of rs12608932, a single-nucleotide polymorphism located in an intron of UNC13A, and risk of ALS and patient survival. METHODS: PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases were systematically searched for genome-wide association studies or case-control studies published up to January 2019 on the association between this variant in UNC13A and risk and/or prognosis of ALS. Data from eligible studies were extracted and analyzed. RESULTS: The pooled data (28,072 patients with sporadic ALS and 56,545 controls) showed that rs12608932(C) was associated with an increased risk of ALS (OR = 1.13, 95%CI 1.07-1.20). Subgroup analysis revealed that rs12608932(C) increased the risk of sporadic ALS in non-Asian individuals, including those from the USA and Europe (OR 1.17, 95%CI 1.10-1.25, P < 0.000), but not in Japanese or Chinese subjects (OR 1.01, 95%CI 0.92-1.10, P = 0.85). The available data demonstrated that the CC genotype decreased the survival time of patients with ALS (OR 1.33, 95%CI 1.19-1.49, P < 0.001). CONCLUSION: The present meta-analysis suggests that rs12608932(C) is associated with increased ALS susceptibility, especially in Caucasian and European subjects, and that the CC genotype of rs12608932 is associated with reduced ALS patient survival.
BACKGROUND:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with both genetic and environmental risk factors. Previous studies trying to find an association between ALS and unc-13 homolog A (UNC13A) gene variants have shown inconsistent results. This study aimed to conduct a meta-analysis of the association between the C allele of rs12608932, a single-nucleotide polymorphism located in an intron of UNC13A, and risk of ALS and patient survival. METHODS: PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases were systematically searched for genome-wide association studies or case-control studies published up to January 2019 on the association between this variant in UNC13A and risk and/or prognosis of ALS. Data from eligible studies were extracted and analyzed. RESULTS: The pooled data (28,072 patients with sporadic ALS and 56,545 controls) showed that rs12608932(C) was associated with an increased risk of ALS (OR = 1.13, 95%CI 1.07-1.20). Subgroup analysis revealed that rs12608932(C) increased the risk of sporadic ALS in non-Asian individuals, including those from the USA and Europe (OR 1.17, 95%CI 1.10-1.25, P < 0.000), but not in Japanese or Chinese subjects (OR 1.01, 95%CI 0.92-1.10, P = 0.85). The available data demonstrated that the CC genotype decreased the survival time of patients with ALS (OR 1.33, 95%CI 1.19-1.49, P < 0.001). CONCLUSION: The present meta-analysis suggests that rs12608932(C) is associated with increased ALS susceptibility, especially in Caucasian and European subjects, and that the CC genotype of rs12608932 is associated with reduced ALSpatient survival.
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Authors: X Rosa Ma; Mercedes Prudencio; Yuka Koike; Sarat C Vatsavayai; Garam Kim; Fred Harbinski; Adam Briner; Caitlin M Rodriguez; Caiwei Guo; Tetsuya Akiyama; H Broder Schmidt; Beryl B Cummings; David W Wyatt; Katherine Kurylo; Georgiana Miller; Shila Mekhoubad; Nathan Sallee; Gemechu Mekonnen; Laura Ganser; Jack D Rubien; Karen Jansen-West; Casey N Cook; Sarah Pickles; Björn Oskarsson; Neill R Graff-Radford; Bradley F Boeve; David S Knopman; Ronald C Petersen; Dennis W Dickson; James Shorter; Sua Myong; Eric M Green; William W Seeley; Leonard Petrucelli; Aaron D Gitler Journal: Nature Date: 2022-02-23 Impact factor: 69.504