Case-control study of UCHL1 S18Y variant in Parkinson's disease

A recent meta‐analysis observed a greater significant inverse association of the ubiquitin carboxy‐terminal hydrolase L1 (UCHL1) S18Y variant with Parkinson's disease (PD) for Asian (predominantly Japanese) populations compared with Caucasian populations. We performed an independent case–control study in 335 PD and 341 control subjects with data from a Chinese population to investigate the age‐of‐onset effect of the UCHL1 variant in PD. The Y/Y and Y/S genotypes were less frequent in the PD young‐onset group than in controls and the frequency of the Y alleles was higher in young controls compared to young‐onset PD (age at examination ≤ 65 years; P = 0.003). Multivariate analysis revealed the Y/Y genotype was significantly lower (P = 0.008) in the young‐onset PD (Y/Y vs. S/S: odds ratio [OR]: 0.42; 95% confidence interval [CI]: 0.24, 0.74; S/Y vs. S/S: OR: 0.66, 95% CI: 0.41, 1.08) compared with controls, but this difference was not seen for the late‐onset PD. Kaplan–Meier analysis carried out on PD subjects demonstrated that the Y/Y genotype was associated with a later onset of PD than Y/S plus S/S genotypes (P = 0.05). We provided an independent confirmation of the protective effect of the UCHL1 S18Y variant (Y/Y genotype) against PD in young Chinese subjects. Further functional studies of the S18Y variant in both cell and animal models will be of interest. © 2006 Movement Disorder Society