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. INTERPRETATION:Based on the current evidence, the UCHL-1 gene does not exhibit a protective effect in PD.
Healy, DG; Abou-Sleiman, PM; Casas, JP; Ahmadi, KR; Lynch, T; Gandhi, S; Muqit, MMK; Foltynie, T; Barker, R; Bhatia, KP; Quinn, NP; Lees, AJ; Gibson, JM; Holton, JL; Revesz, T; Goldstein, DB; Wood, NW
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