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UNC13A variant rs12608932 is associated with increased risk of amyotrophic lateral sclerosis and reduced patient survival: a meta-analysis

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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.

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Funding

This research was supported by the Yunnan Applied Basic Research Project-Union Foundation of China (201801CH00572), National Natural Science Foundation of China (81860247), Yunnan Province Medical Health Research Institute Project (2018NS0102), and The First Affiliated Hospital of Kunming Medical University Doctoral Research Fund Project (2017BS005).

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  1. Baiyuan Yang, Haixia Jiang and Fang Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Seventh People’s Hospital of Chengdu, Chengdu, 690041, Sichuan Province, People’s Republic of China

    Baiyuan Yang

  2. Department of Anesthesia, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan Province, People’s Republic of China

    Haixia Jiang

  3. Department of Geriatric Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan Province, People’s Republic of China

    Fang Wang, Chongmin Wu, Jianjian Bao, Yongyun Zhu, Zhong Xu, Bin Liu, Hui Ren & Xinglong Yang

  4. Department of Anesthesia, Kunming Xishan District People’s Hospital, Kunming, 650100, Yunnan Province, People’s Republic of China

    Shimei Li

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  1. Baiyuan Yang
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Yang, B., Jiang, H., Wang, F. et al. UNC13A variant rs12608932 is associated with increased risk of amyotrophic lateral sclerosis and reduced patient survival: a meta-analysis. Neurol Sci 40, 2293–2302 (2019). https://doi.org/10.1007/s10072-019-03951-y

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