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

Abstract

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±16.2months) than in patients with other genotypes (36.9±19.9months; 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.

Keywords: Amyotrophic lateral sclerosis; BTNL2; Frontotemporal dementia; HLA-DRA/HLA-DRB5; Kaplan-Meier survival curves; Parkinson's disease; RAB38/CTSC.