title: Case-control study of UCHL1 S18Y variant in Parkinson's disease.
abstract: 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 <or= 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.
authors.affiliation: Department of Neurology, Singapore General Hospital, Singapore. gnrtek@sgh.com.sg
authors.forename: Eng-King
authors.initials: EK
authors.lastname: Tan
authors.forename: Kim-Yoong
authors.initials: KY
authors.lastname: Puong
authors.forename: Stephanie
authors.initials: S
authors.lastname: Fook-Chong
authors.forename: Eva
authors.initials: E
authors.lastname: Chua
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Yih
authors.initials: Y
authors.lastname: Yuen
authors.forename: Ratnagopal
authors.initials: R
authors.lastname: Pavanni
authors.forename: Meng-Cheong
authors.initials: MC
authors.lastname: Wong
authors.forename: Kathiravelu
authors.initials: K
authors.lastname: Puvan
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D012016:Reference Values; D012846:Singapore; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase