Exclusion of PINKI 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 PINKI 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 wellcharacterized patients presenting a positive family history of PD in similar to 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 chi(2) test Results: Several common SNPs were identified in our cohorts, including a recently identified coding variant (Q1 15L) in exon I. Genotyping of the Q1 15L variation did not reveal significant frequency differences between patients and controls. Pathogenic mutations in the PINKI gene were not identified, neither in the German nor in the Norwegian cohort. Conclusion: 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.