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.

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.