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Publication Detail
UCHL-1 is not a Parkinson's disease susceptibility gene
  • Publication Type:
    Journal article
  • Publication Sub Type:
    JOUR
  • Authors:
    Healy DG, Abou-Sleiman PM, Casas JP, Ahmadi KR, Lynch T, Gandhi S, Muqit MM, Foltynie T, Barker R, Bhatia KP, Quinn NP, Lees AJ, Gibson JM, Holton JL, Revesz T, Goldstein DB, Wood NW
  • Publication date:
    2006
  • Pagination:
    627, 633
  • Volume:
    59
  • Medium:
    4
  • Print ISSN:
    0364-5134
  • Keywords:
    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
  • Notes:
    Healy, Daniel G Abou-Sleiman, Patrick M Casas, Juan P Ahmadi, Kourosh R Lynch, Timothy Gandhi, Sonia Muqit, Miratul M K Foltynie, Thomas Barker, Roger Bhatia, Kailash P Quinn, Niall P Lees, Andrew J Gibson, J Mark Holton, Janice L Revesz, Tamas Goldstein, David B Wood, Nicholas W Comparative Study Multicenter Study Research Support, Non-U.S. Gov't United States Annals of neurology Ann Neurol. 2006 Apr;59(4):627-33. 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.
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.
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