Recently, Iida et al. discovered a new single-nucleotide polymorphism (SNP) in the ZNF512B gene associated with susceptibility to amyotrophic lateral sclerosis (ALS). The ZNF512B gene was found to be a transcription factor promoting the expression of a downstream gene in the signal transduction pathway of the transforming growth factor-β (TGF-β), which is essential for the protection and survival of neurons but the influence of the new SNP (rs2275294) in actual ALS patients remained unknown. The objective of our study was to examine whether the new SNP in the ZNF512B gene might influence the phenotype of ALS. We conducted a retrospective analysis of the ZNF512B gene in 176 patients diagnosed as having ALS at our hospital. Evaluation of the prognosis after the onset using Kaplan-Meier survival curves in patients with versus without the risk allele (C allele: CC and CT genotypes) revealed a significantly lower survival probability in those with the risk allele (log-rank test, P<0.01), independent of the other prognostic factors in ALS. Our study revealed the influence of the new SNP in actual ALS patients. It would be clinically reasonable to suggest that the ZNF512B gene is a new prognostic factor in ALS. This study is the first, as per our knowledge, to indicate that the association between the new susceptibility gene for ALS and its pathway could be identified.
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