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.
Keywords: Amyotrophic lateral sclerosis; Meta-analysis; Risk; Survival; UNC13A; rs12608932.