1. UNC13A variant rs12608932 is associated with increased risk of amyotrophic lateral sclerosis and reduced patient survival: a meta-analysis.
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Yang, Baiyuan, Jiang, Haixia, Wang, Fang, Li, Shimei, Wu, Chongmin, Bao, Jianjian, Zhu, Yongyun, Xu, Zhong, Liu, Bin, Ren, Hui, and Yang, Xinglong
- Subjects
AMYOTROPHIC lateral sclerosis ,META-analysis ,PROGRESSION-free survival ,SINGLE nucleotide polymorphisms ,DISEASE risk factors ,PROGNOSIS ,GENOTYPES ,RELATIVE medical risk ,RESEARCH ,NERVE tissue proteins ,RESEARCH methodology ,EVALUATION research ,MEDICAL cooperation ,COMPARATIVE studies ,DISEASE susceptibility ,RESEARCH funding - 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. [ABSTRACT FROM AUTHOR]- Published
- 2019
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