Analysis of Lrrk2 R1628P as a risk factor for Parkinson's disease.
Common genetic variants that increase the risk for Parkinson's disease may differentiate patient subgroups and influence future individualized therapeutic strategies. Herein we show evidence for leucine-rich repeat kinase 2 (LRRK2) c.4883G>C (R1628P) as a risk factor in ethnic Chinese populations. A study of 1,986 individuals from 3 independent centers in Taiwan and Singapore demonstrates that Lrrk2 R1628P increases risk for Parkinson's disease (odds ratio, 1.84; 95% confidence interval, 1.20-2.83; p = 0.006). Haplotype analysis suggests an ancestral founder for carriers approximately 2,500 years ago. These findings support the importance of LRRK2 variants in sporadic Parkinson's disease. Ann Neurol 2008.
Ross
Owen A
OA
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA.
Wu
Yih-Ru
YR
Lee
Mei-Ching
MC
Funayama
Manabu
M
Chen
Meng-Ling
ML
Soto
Alexandra I
AI
Mata
Ignacio F
IF
Lee-Chen
Guey-Jen
GJ
Chen
Chiung Mei
CM
Tang
Michelle
M
Zhao
Yi
Y
Hattori
Nobutaka
N
Farrer
Matthew J
MJ
Tan
Eng-King
EK
Wu
Ruey-Meei
RM
D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012846:Singapore / Q000453:epidemiology; D013624:Taiwan / Q000453:epidemiology
D005819:Genetic Markers; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases