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

J Neurol Sci. 2017 Feb 15:373:124-128. doi: 10.1016/j.jns.2016.12.055. Epub 2016 Dec 28.


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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / genetics*
  • Asian People / genetics
  • Butyrophilins / genetics
  • Case-Control Studies
  • Cathepsin C / genetics
  • China
  • Female
  • Genetic Predisposition to Disease*
  • HLA-DR alpha-Chains / genetics*
  • HLA-DRB5 Chains / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide*
  • Proportional Hazards Models
  • Retrospective Studies
  • rab GTP-Binding Proteins / genetics


  • BTNL2 protein, human
  • Butyrophilins
  • HLA-DR alpha-Chains
  • HLA-DRB5 Chains
  • CTSC protein, human
  • Cathepsin C
  • RAB38 protein, human
  • rab GTP-Binding Proteins