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.
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.
Authors: Colin C McCulloch; Denise M Kay; Stewart A Factor; Ali Samii; John G Nutt; Donald S Higgins; Alida Griffith; John W Roberts; Berta C Leis; Jennifer S Montimurro; Cyrus P Zabetian; Haydeh Payami Journal: Hum Genet Date: 2008-01-22 Impact factor: 4.132
Authors: Katherine W Snapinn; Eric B Larson; Hideshi Kawakami; Hiroshi Ujike; Amy R Borenstein; Yuishin Izumi; Ryuji Kaji; Hirofumi Maruyama; Ignacio F Mata; Hiroyuki Morino; Masaya Oda; Debby W Tsuang; Dora Yearout; Karen L Edwards; Cyrus P Zabetian Journal: Parkinsonism Relat Disord Date: 2011-02-22 Impact factor: 4.891
Authors: Kaya Bilguvar; Navneet K Tyagi; Cigdem Ozkara; Beyhan Tuysuz; Mehmet Bakircioglu; Murim Choi; Sakir Delil; Ahmet O Caglayan; Jacob F Baranoski; Ozdem Erturk; Cengiz Yalcinkaya; Murat Karacorlu; Alp Dincer; Michele H Johnson; Shrikant Mane; Sreeganga S Chandra; Angeliki Louvi; Titus J Boggon; Richard P Lifton; Arthur L Horwich; Murat Gunel Journal: Proc Natl Acad Sci U S A Date: 2013-01-28 Impact factor: 11.205
Authors: Carolyn M Hutter; Ali Samii; Stewart A Factor; John G Nutt; Donald S Higgins; Thomas D Bird; Alida Griffith; John W Roberts; Berta C Leis; Jennifer S Montimurro; Denise M Kay; Karen L Edwards; Haydeh Payami; Cyrus P Zabetian Journal: Eur J Neurol Date: 2007-12-18 Impact factor: 6.089
Authors: Cyrus P Zabetian; Carolyn M Hutter; Stewart A Factor; John G Nutt; Donald S Higgins; Alida Griffith; John W Roberts; Berta C Leis; Denise M Kay; Dora Yearout; Jennifer S Montimurro; Karen L Edwards; Ali Samii; Haydeh Payami Journal: Ann Neurol Date: 2007-08 Impact factor: 10.422