Genetic Variation in KIFAP3 Is Associated with an Upper Motor Neuron-Predominant Phenotype in Amyotrophic Lateral Sclerosis

Background: Some authors have recently reported that the CC genotype of single-nucleotide polymorphism (SNP) rs1541160 mapping within the kinesin-associated protein 3 (KIFAP3) gene is associated with increased survival in sporadic amyotrophic lateral sclerosis (sALS). Objective and Methods: The relationship between the rs1541160 genotype and several clinical features of 228 ALS patients was evaluated with the intent of assessing any association between the ALS phenotype and KIFAP3. The SNP rs1541160 within the KIFAP3 expression profile was investigated using real-time PCR in a group of 6 patients harboring the CC genotype and in 12 patients harboring the TT genotype. Results: Analysis of our patients’ clinical features showed that almost half of those with the CC genotype were classified as having upper motor neuron-predominant ALS (UMN-ALS). Conversely, there was an approximately 10% frequency of UMN-ALS in both the TT and the TC patient groups as well as in the entire cohort considered as a whole (p < 0.005). The SNP rs1541160 genotype did not appear to have any effect on patient survival or on KIFAP3 expression. Conclusions: The incidence of the UMN-ALS phenotype in the CC patients of this cohort supports the hypothesis that the SNP rs1541160 within the KIFAP3 gene is a potential modifier of the ALS phenotype.