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


CONCLUSIONS
Based on the current evidence, the UCHL-1 gene does not exhibit a protective effect in PD.
Healy
Daniel G
DG
Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom. danhealy@doctors.org.uk
Abou-Sleiman
Patrick M
PM
Casas
Juan P
JP
Ahmadi
Kourosh R
KR
Lynch
Timothy
T
Gandhi
Sonia
S
Muqit
Miratul M K
MM
Foltynie
Thomas
T
Barker
Roger
R
Bhatia
Kailash P
KP
Quinn
Niall P
NP
Lees
Andrew J
AJ
Gibson
J Mark
JM
Holton
Janice L
JL
Revesz
Tamas
T
Goldstein
David B
DB
Wood
Nicholas W
NW
D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic; D012694:Serine / Q000235:genetics; D014443:Tyrosine / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
C482860:UCHL1 protein, human; D014443:Tyrosine; D012694:Serine; D043222:Ubiquitin Thiolesterase