Mutation analysis and association studies of the UCHL1 gene in German Parkinson's disease patients

Recently, an Ile93Met substitution has been identified in the ubiquitin carboxy-terminal hydrolase LI (UCHL1) gene in a single German PD family with autosomal dominant inheritance. To determine whether mutations in the UCHL1 gene are causative for Parkinson's disease (PD) a detailed mutation analysis was performed in a large sample of German sporadic and familial PD patients. We found no disease-causing mutation in the coding region of the UCHL1 gene. Direct sequencing revealed six intronic polymorphisms in the UCHL1 gene. Analysis of an S18Y polymorphism in exon 3 of the UCHL1 gene in sporadic PD patients and controls showed carriers of allele 2 (tyrosine) significantly less frequent in patients with a reduced risk of 0.57 (CI=0.36-0.88; p=0.012, p(c)=0.047, chi(2)=6.31). Our study shows that sequence variations in the coding region of UCHL1 are a rare event. A protective effect of a certain UCHL1 variant in the pathogenesis of sporadic PD is suggested, underlining the relevance of UCHL1 in neurodegeneration. NeuroReport 11:2079-2082 (C) 2000 Lippincott Williams & Wilkins.