UCHL-1 is not a Parkinson's disease susceptibility gene
Article first published online: 31 JAN 2006
Copyright © 2006 American Neurological Association
Annals of Neurology
Volume 59, Issue 4, pages 627–633, April 2006
How to Cite
Healy, D. G., Abou-Sleiman, P. M., Casas, J. P., Ahmadi, K. R., Lynch, T., Gandhi, S., Muqit, M. M. K., Foltynie, T., Barker, R., Bhatia, K. P., Quinn, N. P., Lees, A. J., Gibson, J. M., Holton, J. L., Revesz, T., Goldstein, D. B. and Wood, N. W. (2006), UCHL-1 is not a Parkinson's disease susceptibility gene. Ann Neurol., 59: 627–633. doi: 10.1002/ana.20757
- Issue published online: 24 MAR 2006
- Article first published online: 31 JAN 2006
- Manuscript Accepted: 24 OCT 2005
- Manuscript Revised: 23 OCT 2005
- Manuscript Received: 13 SEP 2005
- UK Parkinson's Disease Society
- Brain Research Trust
- Royal Society/Wolfson Research Merit Award
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.
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.
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.
Based on the current evidence, the UCHL-1 gene does not exhibit a protective effect in PD. Ann Neurol 2006