UCHL-1 is not a Parkinson's disease susceptibility gene

Ann Neurol. 2006 Apr;59(4):627-33. doi: 10.1002/ana.20757.

Abstract

Objective: The UCHL-1 gene is widely cited as a susceptibility factor for sporadic Parkinson's disease (PD). The strongest evidence comes from a meta-analysis of small studies that reported the S18Y polymorphism as protective against PD, after pooling studies of white and Asian subjects. Here, we present data that challenge this association.

Methods: In a new large case-control study in white individuals (3,023 subjects), the S18Y variant was not protective against PD under any genetic model of inheritance. Similarly, a more powerful haplotype-tagging approach did not detect other associated variants.

Results: Finally, in an updated S18Y-PD meta-analysis (6,594 subjects), no significant association was observed under additive, recessive, or dominant models (odds ratio = 1.00 [95% confidence interval: 0.74-1.33]; odds ratio = 1.01 [95% confidence interval: 0.76-1.35]; and odds ratio = 0.96 [95% confidence interval: 0.86-1.08], respectively), and a cumulative meta-analysis showed a trend toward a null effect.

Interpretation: Based on the current evidence, the UCHL-1 gene does not exhibit a protective effect in PD.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Confidence Intervals
  • Female
  • Genotype
  • Humans
  • Linkage Disequilibrium*
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Odds Ratio
  • Parkinson Disease / genetics*
  • Polymorphism, Genetic*
  • Serine / genetics
  • Tyrosine / genetics
  • Ubiquitin Thiolesterase / genetics*

Substances

  • UCHL1 protein, human
  • Tyrosine
  • Serine
  • Ubiquitin Thiolesterase