title: A polymorphic variation of serine to tyrosine at codon 18 in the ubiquitin C-terminal hydrolase-L1 gene is associated with a reduced risk of sporadic Parkinson's disease in a Japanese population.
abstract: Recent studies suggest that ubiquitin C-terminal hydrolase-L1 (UCH-L1), a neuronal deubiquitinating enzyme, represents a candidate gene responsible for either the development of familial Parkinson's disease (PD) or the protection against sporadic PD in Caucasian populations, although these findings are not fully verified in non-Caucasian populations. To determine an association of the variations in the UCH-L1 gene with development of sporadic PD in a Japanese population, a Ser18Tyr polymorphism and an Ile93Met mutation were studied by PCR-RFLP analysis in 74 Japanese patients with sporadic PD and 155 age-matched non-PD controls. The frequency of 18Tyr allele was significantly lower in PD patients than the controls (38.5% vs. 53.5%) (chi(2)=9.064, p=0.0026; the odds ratio=1.84, 95% confident interval=1.23-2.74). Furthermore, the frequency of 18Tyr/Tyr homozygotes was significantly lower in PD patients than the controls (14.9% vs. 33.5%), compared with that of two other genotypes combined (chi(2)=8.767, p=0.0031; the odds ratio=0.35, 95% confident interval=0.27-0.45). The Ile93Met substitution was not detected in any Japanese subjects examined. These results indicate that the presence of 18Tyr allele and 18Tyr/Tyr homozygosity in the UCH-L1 gene is associated with a reduced risk for development of sporadic PD in a Japanese population, supporting the previous observations on sporadic PD in Caucasian populations.
authors.affiliation: Division of Neurology, Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan. satoj1@post.saga-med.ac.jp
authors.forename: J
authors.initials: J
authors.lastname: Satoh
authors.forename: Y
authors.initials: Y
authors.lastname: Kuroda
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D003062:Codon / Q000235:genetics*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000378:metabolism; D010300:Parkinson Disease / Q000208:ethnology / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D046988:Proteasome Endopeptidase Complex; D012306:Risk; D013869:Thiolester Hydrolases / Q000737:chemistry / Q000235:genetics*; D043222:Ubiquitin Thiolesterase
chemical_list: D003062:Codon; D009097:Multienzyme Complexes; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex