HLA-DRA/HLA-DRB5 polymorphism affects risk of sporadic ALS and survival in a southwest Chinese cohort

Introduction Frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) are neurodegenerative diseases that share common genetic risk factors. A recent genome-wide association study has linked risk of FTD with polymorphisms in the HLA-DRA/HLA-DRB5 gene (rs9268877, rs9268856), BTNL2 gene (rs1980493), and RAB38/CTSC gene (rs302668). Methods We used the SNPscan™ Kit to genotype these variants in 400 Chinese patients with sporadic ALS, 554 with sporadic PD and 634 healthy controls. Results The AA genotype at rs9268856 increased risk of ALS (P = 0.005). Mean survival time was significantly shorter in patients with the AA genotype (24.8 ± 16.2 months) than in patients with other genotypes (36.9 ± 19.9 months; P < 0.001). Kaplan-Meier curves and Cox analysis indicated significantly lower survival probability for patients carrying the AA genotype (P < 0.001). Conclusion Our results suggest that the AA genotype at rs9268856 is an independent risk factor and prognostic factor for ALS in Han Chinese from southwest China.