Association of progranulin polymorphism rs5848 with neurodegenerative diseases: a meta-analysis

J Neurol. 2015;262(4):814-22. doi: 10.1007/s00415-014-7630-2. Epub 2015 Jan 13.


The purpose of this meta-analysis was to investigate the association between progranulin polymorphism rs5848 and risk of the neurodegenerative diseases frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Published literature from PubMed and other databases were retrieved, and 16 case-control studies were identified as eligible: 5 on FTLD (1,439 cases, 4,461 controls), 5 on AD (2,502 cases, 2,162 controls), 3 on PD (1,605 cases, 1,591 controls), and 3 on ALS (663 cases, 811 controls). The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated. We found that rs5848 was associated with an increased risk of neurodegenerative diseases in the homozygous (TT vs. CC: OR, 1.24; 95% CI, 1.10-1.39; P < 0.001) and recessive models (TT vs. CC + CT: OR, 1.23; 95% CI, 1.10-1.37; P < 0.001). Stratified analyses showed associations of rs5848 with increased risk of AD and PD in the homozygous and recessive models. Our data indicate that rs5848 is associated with risk of AD and PD, suggesting important roles of progranulin in neurodegenerative processes.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Amyotrophic Lateral Sclerosis / genetics*
  • Frontotemporal Lobar Degeneration / genetics*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide
  • Progranulins


  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins