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 L1 (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, chi2 = 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.
Department of Molecular Human Genetics, Ruhr-University Bochum, Germany.
P
P
Wintermeyer
R
R
Krüger
W
W
Kuhn
T
T
Müller
D
D
Woitalla
D
D
Berg
G
G
Becker
E
E
Leroy
M
M
Polymeropoulos
K
K
Berger
H
H
Przuntek
L
L
Schöls
J T
JT
Epplen
O
O
Riess
D000368:Aged; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005260:Female; D005799:Genes, Dominant; D006580:Genetic Carrier Screening; D005838:Genotype; D005858:Germany; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics*; D011110:Polymorphism, Genetic; D012016:Reference Values; D015183:Restriction Mapping; D013869:Thiolester Hydrolases / Q000235:genetics*; D043222:Ubiquitin Thiolesterase; D044465:White People
D017931:DNA Primers; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase