Genetic association study of PINK1 coding polymorphisms in Parkinson's disease.
Parkinson's disease (PD) is the most common neurodegenerative movement disorder with a substantial genetic component (which is more pronounced in earlier onset cases). In addition to three well-confirmed PD genes (SNCA, parkin and DJ-1), mutations in the PTEN Induced Kinase (PINK1) gene have recently been identified in families with recessive early onset PD. We tested the hypothesis that three common coding variations (Leu63Leu, Ala340Thr and Asn521Thr) could increase the risk of PD. We performed a case control association study in a series of 91 PD cases (Caucasian of Canadian origin) and 182 normal controls. The patients were largely pre-selected for having an early age of onset (<50 years) and/or a positive family history. Our results did not reveal any evidence of association between PD and any of the three SNPs at the allelic or genotypic levels (p > 0.25). Furthermore, we did not detect a modifying effect for any genotype upon the age of onset in the PD group (p > 0.19). Nevertheless, it remains to be evaluated whether PINK1 variations contribute to the risk of common late onset sporadic PD.
Groen
Justus L
JL
Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, 6 Queen's Park Crescent West, Toronto, Ont., Canada M5S 3H2.
Kawarai
Toshitaka
T
Toulina
Anna
A
Rivoiro
Chiara
C
Salehi-Rad
Shabnam
S
Sato
Christine
C
Morgan
Angharad
A
Liang
Yan
Y
Postuma
Ronald B
RB
St George-Hyslop
Peter
P
Lang
Anthony E
AE
Rogaeva
Ekaterina
E
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099202:PTEN-Induced Putative Kinase
D004247:DNA; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase