A polymorphic variation of serine to tyrosine at codon 18 in the ubiquitinC-terminal hydrolase-L1 gene is associated with a reduced risk of sporadicParkinson's disease in a Japanese population

Recent studies suggest that ubiquitin C-terminal hydrolase-L1 (UCH-L1), a n euronal deubiquitinating enzyme, represents a candidate gene responsible fo r either the development of familial Parkinson's disease (PD) or the protec tion against sporadic PD in Caucasian populations, although these findings are not fully verified in non-Caucasian populations. To determine an associ ation 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 sign ificantly 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 significant ly 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 substituti on was not detected in any Japanese subjects examined. These results indica te 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. (C) 2001 Elsevier Science B.V. All rights reserv ed.