Association analysis of the GRN rs5848 and MAPT rs242557 polymorphisms in Parkinson's disease and multiple system atrophy: a large-scale population-based study and meta-analysis

Int J Neurosci. 2016 Oct;126(10):947-54. doi: 10.3109/00207454.2015.1086345. Epub 2015 Sep 17.

Abstract

Background: Previous studies have found an association between the granulin gene rs5848 and microtubule-associated protein tau gene (MAPT) rs242557 polymorphisms and susceptibility to Parkinson's disease (PD). However, the results of association studies between the two polymorphisms and PD have been inconsistent. Given the overlap in clinical and pathological characteristics of PD and multiple system atrophy (MSA), we examined the associations of these two polymorphisms with PD and MSA in a subset of the Chinese population.

Methods: In total, 1270 PD patients, 360 MSA patients and 830 healthy controls (HCs) were included in the study. All subjects were genotyped for the two polymorphisms using Sequenom iPLEX Assay technology. After combining our results with the available published data, a meta-analysis was conducted to investigate the association between MAPT rs242557 and the risk of PD.

Results: The minor allele "T" of GRN rs5848 decreased the risk for PD (p = 0.0309, odds radio [OR], 0.86; 95% CI, 0.76-0.99). No differences in the genotype distributions and minor allele frequency (MAF) of MAPT rs242557 were observed between the PD and the HCs in our Chinese population. Our meta-analysis revealed an association between MAPT rs242557 and PD in Caucasian and Asian population in a recessive model (p = 0.049 and p = 0.046, respectively). However, no significant differences in the genotype distributions and MAFs of the two polymorphisms were found between the MSA patients and HCs.

Conclusion: Our results indicate that GRN rs5458 may decrease the risk of PD in Chinese individuals, and the MAPT rs242557 is marginally associated with PD.

Keywords: GRN  rs5848; MAPT rs242557; Parkinson's disease; meta-analysis; multiple system atrophy; polymorphisms.

Publication types

  • Meta-Analysis

MeSH terms

  • China
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Multiple System Atrophy / genetics*
  • Parkinson Disease / genetics*
  • Polymorphism, Genetic
  • Progranulins
  • tau Proteins / genetics*

Substances

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