Exclusion of PINK1 as candidate gene for the late-onset form of Parkinson's disease in two European populations.
BACKGROUND
Parkinson's disease (PD) is the second most common neurodegenerative disorder. Recently, mutations in the PINK1 (PARK6) gene were shown to rarely cause autosomal-recessively transmitted, early-onset parkinsonism. In order to evaluate whether PINK1 contributes to the risk of common late-onset PD we analysed PINK1 sequence variations. A German (85 patients) and a Norwegian cohort (90 patients) suffering from late-onset PD were screened for mutations and single nucleotide polymorphisms (SNPs) in the PINK1 gene. Both cohorts consist of well-characterized patients presenting a positive family history of PD in approximately 17%. Investigations were performed by single strand conformation polymorphism (SSCP), denaturating high performance liquid chromatography (DHPLC) and sequencing analyses. SNP frequencies were compared by the chi2 test.


RESULTS
Several common SNPs were identified in our cohorts, including a recently identified coding variant (Q115L) in exon 1. Genotyping of the Q115L variation did not reveal significant frequency differences between patients and controls. Pathogenic mutations in the PINK1 gene were not identified, neither in the German nor in the Norwegian cohort.


CONCLUSIONS
Sequence variation in the PINK1 gene appears to play a marginal quantitative role in the pathogenesis of the late-onset form of PD, in German and Norwegian cohorts, if at all.
Schlitter
Anna Melissa
AM
Department of Human Genetics, Ruhr-University Bochum, Germany. schlitter@gmx.net
Kurz
Martin
M
Larsen
Jan P
JP
Woitalla
Dirk
D
Mueller
Thomas
T
Epplen
Joerg T
JT
Dekomien
Gabriele
G
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D015331:Cohort Studies; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D005973:Glutamine / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009664:Norway / Q000453:epidemiology; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
D005973:Glutamine; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase