Genetic variants in GAPDH confer susceptibility to sporadic Parkinson's disease in a Chinese Han population

PLoS One. 2015 Aug 10;10(8):e0135425. doi: 10.1371/journal.pone.0135425. eCollection 2015.

Abstract

Background: Accumulating evidence has demonstrated that the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a part of Lewy body inclusions and involves the pathogenesis of Parkinson's disease (PD). However, it remains unknown whether or not genetic variation at the GAPDH locus contributes to the risk for PD.

Methods: A total of 302 sporadic PD patients and 377 control subjects were recruited in our study for assessing two single nucleotide polymorphisms (rs3741918 and rs1060619) in the GAPDH gene. Both allelic association and additive models were used to analyze association between GAPDH variants and risk for PD.

Results: Both polymorphisms were significantly associated with risk for PD after correction by Bonferroni multiple testing. The minor allele of rs3741918 was associated with decreased risk of sporadic PD (allelic contrast, OR = 0.74, 95% CI: 0.59-0.93, corrected P = 0.028; additive model, OR = 0.73, 95% CI: 0.58-0.92, corrected P = 0.018). While for the rs1060619 locus, the minor allele conferred increased risk for PD (allelic contrast, OR = 1.41, 95% CI: 1.14-1.75, corrected P = 0.007; additive model, OR = 1.43, 95% CI: 1.15-1.79, corrected P = 0.002).

Conclusion: Our study indicates that GAPDH variants confer susceptibility to sporadic PD in a Chinese Han population, which is consistent with the role of GAPDH protein in neuronal apoptosis. To our knowledge, this is the first study of genetic association between GAPDH locus and risk for PD in the Chinese population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Case-Control Studies
  • Female
  • Gene Expression
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Glyceraldehyde-3-Phosphate Dehydrogenases / genetics*
  • Humans
  • Lewy Bodies / chemistry
  • Lewy Bodies / enzymology
  • Male
  • Middle Aged
  • Models, Genetic
  • Parkinson Disease / diagnosis
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology
  • Polymorphism, Single Nucleotide*

Substances

  • Glyceraldehyde-3-Phosphate Dehydrogenases

Grants and funding

This study was supported by the National Natural Science Foundation of China (No. 81471305 and 31171211 to TW, No. 81200983 to NX, No. 81301082 to JH), China Medical Foundation (No. 2012B09 to NX) and Hubei Molecular Imaging Key Laboratory (No. 0203201343 to NX). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.