Variants in the LRRK1 gene and susceptibility to Parkinson's disease in Norway.
The discovery of LRRK2 gene mutations in late-onset Parkinson's disease (PD) has irrevocably established the role of genetics in the etiology of PD. The LRRK1 gene is the single homolog of LRRK2. A high degree of homology exists between LRRK1 and LRRK2, indicative of shared functions and/or pathways. One study has examined LRRK1 in familial parkinsonism by complete sequencing of the gene, reporting 4 novel non-synonymous coding variants within the LRRK1 gene. One of these variants (ss65713826) was identified in a Norwegian proband. We investigated whether five common polymorphisms or these recently identified coding changes within LRRK1 are associated with PD in the Norwegian population. Two rare coding variants ss65713826 and ss65713830 were more frequent in patients than controls. However, their identification in healthy controls and lack of co-segregation with disease suggests they may represent benign polymorphisms.
Haugarvoll
Kristoffer
K
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA, and Department of Neurology, St. Olav's Hospital, Trondheim, Norway. haugarvoll.kristoffer@mayo.edu
Toft
Mathias
M
Ross
Owen A
OA
White
Linda R
LR
Aasly
Jan O
JO
Farrer
Matthew J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000208:ethnology; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
D018698:Glutamic Acid; C510751:LRRK1 protein, human; D017346:Protein Serine-Threonine Kinases; D008239:Lysine